首页 > 最新文献

Expert Review of Clinical Pharmacology最新文献

英文 中文
Clozapine for persons with neurodevelopmental disorders: a systematic review and expert recommendations for clinical practice. 用于神经发育障碍患者的氯氮平:系统综述和临床实践专家建议。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-03 DOI: 10.1080/17512433.2024.2410395
Hélène Verdoux, Clélia Quiles, Jose de Leon

Introduction: We aimed to synthesize the information on the risks and benefits of clozapine prescription for resistant challenging behavior in persons with neurodevelopmental disorders.

Methods: Articles were identified with MEDLINE, Web of Sciences, and PsycINFO search from inception through January 2024. The review was restricted to persons with intellectual disability (ID) and/or autism spectrum disorder (ASD) without comorbid psychotic or affective disorder. Data were synthesized narratively.

Results: We identified 24 articles (13 case reports, eight chart studies, two controlled studies, one pharmaco-epidemiological study) including 296 patients with ID (n = 222) or ASD (n = 74) (10% aged ≤ 18 years). After clozapine initiation, a decreased frequency of challenging behavior persisting over time was reported in most participants included in clinical studies, and a significant reduction in the number of admissions in the population-based two-year mirror-image study. Adverse drug reactions were those commonly observed with clozapine, i.e. constipation, sedation, and weight gain.

Conclusions: Since only four participants were included in the controlled studies, the benefits of clozapine in neurodevelopmental disorders are supported by a body of evidence exclusively drawn from observational studies. Further studies are required to clarify the indications of clozapine with respect to the unmet need induced by resistant challenging behavior.

Registration: PROSPERO database registration number CRD42024522343.

简介我们旨在综合有关氯氮平处方治疗神经发育障碍患者耐受性挑战行为的风险和益处的信息:通过MEDLINE、Web of Sciences和PsycINFO检索发现了从开始到2024年1月的文章。研究对象仅限于智力障碍(ID)和/或自闭症谱系障碍(ASD)患者,且不合并精神病或情感障碍。对数据进行了叙述性综合:我们发现了 24 篇文章(13 篇病例报告、8 篇图表研究、2 篇对照研究、1 篇药物流行病学研究),其中包括 296 名智障患者(n = 222)或自闭症谱系障碍患者(n = 74)(10% 年龄小于 18 岁)。据报道,在开始使用氯氮平之后,大多数参与临床研究的患者在一段时间内持续出现挑战性行为的频率有所降低,而在为期两年的人群镜像研究中,入院人数也显著减少。药物不良反应是氯氮平常见的不良反应,如便秘、镇静、体重增加等:由于只有四名参与者参与了对照研究,因此氯氮平对神经发育障碍的益处得到了大量证据的支持,这些证据完全来自观察性研究。还需要进一步的研究,以明确氯氮平在抵抗性挑战行为引起的未满足需求方面的适应症:PROSPERO数据库注册号为CRD42024522343。
{"title":"Clozapine for persons with neurodevelopmental disorders: a systematic review and expert recommendations for clinical practice.","authors":"Hélène Verdoux, Clélia Quiles, Jose de Leon","doi":"10.1080/17512433.2024.2410395","DOIUrl":"10.1080/17512433.2024.2410395","url":null,"abstract":"<p><strong>Introduction: </strong>We aimed to synthesize the information on the risks and benefits of clozapine prescription for resistant challenging behavior in persons with neurodevelopmental disorders.</p><p><strong>Methods: </strong>Articles were identified with MEDLINE, Web of Sciences, and PsycINFO search from inception through January 2024. The review was restricted to persons with intellectual disability (ID) and/or autism spectrum disorder (ASD) without comorbid psychotic or affective disorder. Data were synthesized narratively.</p><p><strong>Results: </strong>We identified 24 articles (13 case reports, eight chart studies, two controlled studies, one pharmaco-epidemiological study) including 296 patients with ID (<i>n</i> = 222) or ASD (<i>n</i> = 74) (10% aged ≤ 18 years). After clozapine initiation, a decreased frequency of challenging behavior persisting over time was reported in most participants included in clinical studies, and a significant reduction in the number of admissions in the population-based two-year mirror-image study. Adverse drug reactions were those commonly observed with clozapine, i.e. constipation, sedation, and weight gain.</p><p><strong>Conclusions: </strong>Since only four participants were included in the controlled studies, the benefits of clozapine in neurodevelopmental disorders are supported by a body of evidence exclusively drawn from observational studies. Further studies are required to clarify the indications of clozapine with respect to the unmet need induced by resistant challenging behavior.</p><p><strong>Registration: </strong>PROSPERO database registration number CRD42024522343.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effectiveness of ulinastatin in critical care patients in real world: a retrospective multi-center study. 乌利那他汀在重症监护患者中的实际疗效:一项多中心回顾性研究。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-03 DOI: 10.1080/17512433.2024.2402433
Deduo Xu, Yi Shan, Qinghua Liu, Pei Liang, Xin Hao, Jinyuan Zhang, Ze Yu, Wenfang Li, Fei Gao, Xia Tao, Qin Gu, Yabin Ma, Wansheng Chen

Objectives: Ulinastatin has been applied in various diseases associated with inflammation, but its effectiveness lacks real-world evidence. We aimed to evaluate the effectiveness of ulinastatin based on a real-world database in the intensive care unit (ICU) patients.

Methods: This was a retrospective cohort study. ICU patient data from multi-centers in China were collected. Propensity score matching (PSM) was applied. The effectiveness of ulinastatin was evaluated by mortality, length of stay in the ICU and mechanical ventilation duration. Kaplan-Meier method was used to estimate the hazard ratio and plot the survival curve.

Results: A total of 2036 patients were analyzed after PSM. Mortality was significantly lower in the ulinastatin group than in the non-ulinastatin group (hazard ratio for death: 0.77; 95% confidence interval: 0.62-0.96; p = 0.018). Ulinastatin significantly reduced mortality at 28 days (10.0% vs. 13.6%), 60 days (13.9% vs. 18.2%) and 90 days (14.7% vs. 18.5%), length of stay in the ICU (median 8.0 d vs. 13.0 d), and mechanical ventilation duration (median 24.0 h vs. 25.0 h; p < 0.05).

Conclusions: Ulinastatin was beneficial for patients in the ICU, mainly by reducing mortality, length of ICU stay, and mechanical ventilation duration. This study provides evidence of the clinical effectiveness of ulinastatin.

研究目的乌利那他汀已被应用于多种与炎症相关的疾病,但其有效性缺乏真实世界的证据。我们的目的是根据重症监护室(ICU)患者的实际数据库评估乌利那他汀的疗效:这是一项回顾性队列研究。方法:这是一项回顾性队列研究,收集了来自中国多个中心的 ICU 患者数据。采用倾向得分匹配法(PSM)。通过死亡率、ICU住院时间和机械通气时间评估乌利那他汀的疗效。采用卡普兰-梅耶法估算危险比并绘制生存曲线:结果:共分析了 2036 名 PSM 患者。乌利那他汀组的死亡率明显低于非乌利那他汀组(死亡危险比:0.77;95% 置信区间:0.62-0.96;P = 0.018)。乌利那他汀能明显降低28天(10.0% vs. 13.6%)、60天(13.9% vs. 18.2%)和90天(14.7% vs. 18.5%)的死亡率、重症监护室住院时间(中位数8.0天 vs. 13.0天)和机械通气时间(中位数24.0小时 vs. 25.0小时;P 结论:乌利那他汀能明显降低重症监护室住院时间(中位数8.0天 vs. 13.0天)和机械通气时间(中位数24.0小时 vs. 25.0小时):乌利那他汀对重症监护病房的患者有益,主要是降低了死亡率、缩短了重症监护病房的住院时间和机械通气时间。这项研究为乌利那他汀的临床疗效提供了证据。
{"title":"Effectiveness of ulinastatin in critical care patients in real world: a retrospective multi-center study.","authors":"Deduo Xu, Yi Shan, Qinghua Liu, Pei Liang, Xin Hao, Jinyuan Zhang, Ze Yu, Wenfang Li, Fei Gao, Xia Tao, Qin Gu, Yabin Ma, Wansheng Chen","doi":"10.1080/17512433.2024.2402433","DOIUrl":"10.1080/17512433.2024.2402433","url":null,"abstract":"<p><strong>Objectives: </strong>Ulinastatin has been applied in various diseases associated with inflammation, but its effectiveness lacks real-world evidence. We aimed to evaluate the effectiveness of ulinastatin based on a real-world database in the intensive care unit (ICU) patients.</p><p><strong>Methods: </strong>This was a retrospective cohort study. ICU patient data from multi-centers in China were collected. Propensity score matching (PSM) was applied. The effectiveness of ulinastatin was evaluated by mortality, length of stay in the ICU and mechanical ventilation duration. Kaplan-Meier method was used to estimate the hazard ratio and plot the survival curve.</p><p><strong>Results: </strong>A total of 2036 patients were analyzed after PSM. Mortality was significantly lower in the ulinastatin group than in the non-ulinastatin group (hazard ratio for death: 0.77; 95% confidence interval: 0.62-0.96; <i>p</i> = 0.018). Ulinastatin significantly reduced mortality at 28 days (10.0% vs. 13.6%), 60 days (13.9% vs. 18.2%) and 90 days (14.7% vs. 18.5%), length of stay in the ICU (median 8.0 d vs. 13.0 d), and mechanical ventilation duration (median 24.0 h vs. 25.0 h; <i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>Ulinastatin was beneficial for patients in the ICU, mainly by reducing mortality, length of ICU stay, and mechanical ventilation duration. This study provides evidence of the clinical effectiveness of ulinastatin.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pharmacokinetic interaction of quetiapine and lamotrigine - victim and perpetrator? 喹硫平与拉莫三嗪的药代动力学相互作用--受害者还是肇事者?
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-03 DOI: 10.1080/17512433.2024.2410400
Florian Gilleßen, Arnim Johannes Gaebler, Ekkehard Haen, Georgios Schoretsanitis, Justyna Wozniak, Julia C Stingl, Michael Paulzen

Objective: We aimed to investigate the ambiguous findings of earlier research regarding the reduction of quetiapine plasma levels when combined with lamotrigine, most likely via UDP-glucuronosyltransferase induction by lamotrigine.

Methods: One thousand one hundred and fifty samples, divided into four groups of patients receiving either quetiapine immediate- (IR) or extended-release (XR) without or in combination with lamotrigine were compared regarding absolute and dose-adjusted plasma concentrations. Furthermore, samples of intra-individual controls were analyzed.

Results: Patients receiving quetiapine IR in combination with lamotrigine showed 31% lower plasma (p = 0.002) and 23% lower dose-adjusted plasma concentrations (p = 0.004) compared to those receiving IR monotherapy. The proportion of patients with quetiapine plasma concentrations below the lower limit of the therapeutic reference range was 50% and 30% in the combination group and in patients receiving monotherapy, respectively (p = 0.03). However, no significant differences regarding plasma concentration (p = 0.13) and dose-adjusted plasma concentration (p = 0.42) were observed in patients with combination vs. monotherapy with the XR formulation of quetiapine. In the intra-individual controls, no trends could be identified, possibly due to insufficient number of samples (p > 0.05).

Conclusions: The combination of quetiapine IR with lamotrigine is associated with significantly lower drug concentrations of quetiapine, potentially impacting quetiapine effectiveness. For quetiapine ER, a significant interaction is less likely.

研究目的我们旨在研究早期研究中关于喹硫平与拉莫三嗪合用时血浆中喹硫平水平降低的模糊结论,这很可能是通过拉莫三嗪诱导UDP-葡萄糖醛酸转移酶所致:将接受喹硫平即释(IR)或缓释(XR)治疗但不与拉莫三嗪合用或与拉莫三嗪合用的患者分成四组,对一千一百五十份样本的绝对血浆浓度和剂量调整血浆浓度进行了比较。此外,还分析了个体内对照样本:结果:与接受IR单药治疗的患者相比,接受喹硫平IR联合拉莫三嗪治疗的患者血浆浓度低31%(p = 0.002),剂量调整后血浆浓度低23%(p = 0.004)。联合用药组和单药治疗组中,喹硫平血浆浓度低于治疗参考范围下限的患者比例分别为50%和30%(p = 0.03)。然而,在接受喹硫平XR制剂联合治疗与单药治疗的患者中,未观察到血浆浓度(p = 0.13)和剂量调整血浆浓度(p = 0.42)方面的明显差异。在个体内部对照中,可能由于样本数量不足(p > 0.05),未发现任何趋势:结论:喹硫平IR与拉莫三嗪合用时,喹硫平的药物浓度明显降低,可能会影响喹硫平的疗效。对于喹硫平 ER 而言,发生显著相互作用的可能性较小。
{"title":"Pharmacokinetic interaction of quetiapine and lamotrigine - victim and perpetrator?","authors":"Florian Gilleßen, Arnim Johannes Gaebler, Ekkehard Haen, Georgios Schoretsanitis, Justyna Wozniak, Julia C Stingl, Michael Paulzen","doi":"10.1080/17512433.2024.2410400","DOIUrl":"10.1080/17512433.2024.2410400","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to investigate the ambiguous findings of earlier research regarding the reduction of quetiapine plasma levels when combined with lamotrigine, most likely via UDP-glucuronosyltransferase induction by lamotrigine.</p><p><strong>Methods: </strong>One thousand one hundred and fifty samples, divided into four groups of patients receiving either quetiapine immediate- (IR) or extended-release (XR) without or in combination with lamotrigine were compared regarding absolute and dose-adjusted plasma concentrations. Furthermore, samples of intra-individual controls were analyzed.</p><p><strong>Results: </strong>Patients receiving quetiapine IR in combination with lamotrigine showed 31% lower plasma (<i>p</i> = 0.002) and 23% lower dose-adjusted plasma concentrations (<i>p</i> = 0.004) compared to those receiving IR monotherapy. The proportion of patients with quetiapine plasma concentrations below the lower limit of the therapeutic reference range was 50% and 30% in the combination group and in patients receiving monotherapy, respectively (<i>p</i> = 0.03). However, no significant differences regarding plasma concentration (<i>p</i> = 0.13) and dose-adjusted plasma concentration (<i>p</i> = 0.42) were observed in patients with combination vs. monotherapy with the XR formulation of quetiapine. In the intra-individual controls, no trends could be identified, possibly due to insufficient number of samples (<i>p</i> > 0.05).</p><p><strong>Conclusions: </strong>The combination of quetiapine IR with lamotrigine is associated with significantly lower drug concentrations of quetiapine, potentially impacting quetiapine effectiveness. For quetiapine ER, a significant interaction is less likely.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Is therapeutic drug monitoring a dancing partner for TNF-α inhibitors in real-world practice? Answers from an updated systematic review and meta-analysis. 治疗药物监测是 TNF-α 抑制剂在实际应用中的舞伴吗?最新系统综述和荟萃分析给出的答案。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-01 Epub Date: 2024-09-21
Yang Hu, Zaiwei Song, Yuan Gao, Dan Jiang, Yiwen Ran, Yi Ma, Huibo Li, Rongsheng Zhao

Introduction: This systematic review aimed to determine the effect of therapeutic drug monitoring (TDM) for tumor necrosis factor-α inhibitors (TNF-αI) in immune-mediated inflammatory diseases (IMIDs) based on real-world evidence, as results from published meta-analyses based on randomized controlled trials (RCTs) may not fully capture the nuances of clinical practice due to strict criteria.

Methods: We searched PubMed, Embase, and the Cochrane Library up to 1 August 2023. Cohort studies comparing TDM (proactive and reactive) with empirical management were included. Primary outcome was effectiveness [for IBDs: clinical remission; for rheumatic diseases: clinical remission or low disease activity], with certainty of evidence appraised using the GRADE approach. Secondary outcomes included treatment failure, serious adverse events (SAEs), IMIDs-related surgeries or hospitalizations, and anti-drug antibodies (ADAs) development risk.

Results: Twenty-four cohort studies were included and almost all were on infliximab. For IBDs, compared with empirical management, proactive TDM significantly improved clinical remission (RR = 1.15, 95% CI = 1.04-1.28), reduced IBDs-related surgeries (RR = 0.46, 95% CI = 0.26-0.81), hospitalizations (RR = 0.60, 95% CI = 0.43-0.83), SAEs (RR = 0.23, 95% CI = 0.07-0.76), and ADAs development risk (RR = 0.34, 95% CI = 0.19-0.60). Reactive TDM significantly lowered hospitalization rates and might be cost-effective. Proactive TDM outperformed reactive TDM in secondary outcomes. For rheumatic diseases, benefits of TDM were inconclusive due to limited evidence.

Conclusions: Real-world evidence supports proactive TDM of TNF-αI (particularly infliximab) in IBDs to improve effectiveness, safety, and immunogenicity. However, benefits of TDM for different TNF-αI in other IMIDs remain uncertain.

Protocol registration: www.crd.york.ac.uk/ PROSPERO identifier is CRD42022370846.

导言:由于基于随机对照试验(RCT)的已发表荟萃分析的结果可能因严格的标准而无法完全反映临床实践的细微差别,因此本系统综述旨在根据现实世界的证据确定肿瘤坏死因子-α抑制剂(TNF-αI)治疗药物监测(TDM)在免疫介导的炎症性疾病(IMIDs)中的效果:我们检索了截至 2023 年 8 月 1 日的 PubMed、Embase 和 Cochrane 图书馆。方法:我们检索了截至 2023 年 8 月 1 日的 PubM、Embase 和 Cochrane 图书馆,纳入了比较 TDM(主动和被动)与经验性管理的队列研究。主要结果为有效性[对于IBD:临床缓解;对于风湿性疾病:临床缓解或低疾病活动性],采用GRADE方法评估证据的确定性。次要结果包括治疗失败、严重不良事件(SAEs)、IMIDs相关手术或住院以及抗药抗体(ADAs)发展风险:结果:共纳入了 24 项队列研究,几乎所有研究都涉及英夫利西单抗。对于 IBDs,与经验性治疗相比,主动性 TDM 可显著改善临床缓解(RR = 1.15,95% CI = 1.04-1.28),减少 IBDs 相关手术(RR = 0.46,95% CI = 0.26-0.81)、住院(RR = 0.60,95% CI = 0.43-0.83)、SAEs(RR = 0.23,95% CI = 0.07-0.76)和 ADAs 发展风险(RR = 0.34,95% CI = 0.19-0.60)。反应性 TDM 能明显降低住院率,可能具有成本效益。在次要结果方面,主动式TDM优于被动式TDM。对于风湿性疾病,由于证据有限,TDM的益处尚无定论:真实世界的证据支持对IBD患者的TNF-αI(尤其是英夫利西单抗)进行主动TDM,以提高有效性、安全性和免疫原性。然而,TDM对其他IMIDs中不同TNF-αI的益处仍不确定。协议注册:www.crd.york.ac.uk/ PROSPERO标识符为CRD42022370846。
{"title":"Is therapeutic drug monitoring a dancing partner for TNF-α inhibitors in real-world practice? Answers from an updated systematic review and meta-analysis.","authors":"Yang Hu, Zaiwei Song, Yuan Gao, Dan Jiang, Yiwen Ran, Yi Ma, Huibo Li, Rongsheng Zhao","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>This systematic review aimed to determine the effect of therapeutic drug monitoring (TDM) for tumor necrosis factor-α inhibitors (TNF-αI) in immune-mediated inflammatory diseases (IMIDs) based on real-world evidence, as results from published meta-analyses based on randomized controlled trials (RCTs) may not fully capture the nuances of clinical practice due to strict criteria.</p><p><strong>Methods: </strong>We searched PubMed, Embase, and the Cochrane Library up to 1 August 2023. Cohort studies comparing TDM (proactive and reactive) with empirical management were included. Primary outcome was effectiveness [for IBDs: clinical remission; for rheumatic diseases: clinical remission or low disease activity], with certainty of evidence appraised using the GRADE approach. Secondary outcomes included treatment failure, serious adverse events (SAEs), IMIDs-related surgeries or hospitalizations, and anti-drug antibodies (ADAs) development risk.</p><p><strong>Results: </strong>Twenty-four cohort studies were included and almost all were on infliximab. For IBDs, compared with empirical management, proactive TDM significantly improved clinical remission (RR = 1.15, 95% CI = 1.04-1.28), reduced IBDs-related surgeries (RR = 0.46, 95% CI = 0.26-0.81), hospitalizations (RR = 0.60, 95% CI = 0.43-0.83), SAEs (RR = 0.23, 95% CI = 0.07-0.76), and ADAs development risk (RR = 0.34, 95% CI = 0.19-0.60). Reactive TDM significantly lowered hospitalization rates and might be cost-effective. Proactive TDM outperformed reactive TDM in secondary outcomes. For rheumatic diseases, benefits of TDM were inconclusive due to limited evidence.</p><p><strong>Conclusions: </strong>Real-world evidence supports proactive TDM of TNF-αI (particularly infliximab) in IBDs to improve effectiveness, safety, and immunogenicity. However, benefits of TDM for different TNF-αI in other IMIDs remain uncertain.</p><p><strong>Protocol registration: </strong>www.crd.york.ac.uk/ PROSPERO identifier is CRD42022370846.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Population pharmacokinetics of nirmatrelvir/ritonavir in critically ill Chinese COVID-19 patients and recommendations for medication use: a two-center retrospective study. 中国 COVID-19 重症患者中尼马瑞韦/利托那韦的群体药代动力学及用药建议:一项双中心回顾性研究。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-30 DOI: 10.1080/17512433.2024.2410385
Junjun Xu, Jinmeng Li, Meng Chen, Huifang Jiang, Xudong Fan, Yangmin Hu, Haili Shan, Mingdong Yang, Yichao Xu, Yuying Lang, Haibin Dai, Xinjun Cai

Background: This study aimed to establish population pharmacokinetics (PPK) models of nirmatrelvir/ritonavir in critically ill Chinese patients with the coronavirus disease 2019 (COVID-19) infection, explore factors affecting the pharmacokinetics (PK) of nirmatrelvir/ritonavir.

Methods: A total of 285 serum samples and clinical data were collected from 152 patients. The PPK models of nirmatrelvir/ritonavir were analyzed using nonlinear mixed-effect modeling (NONMEM) approach. The optimal dosing regimen for patients with different renal function was determined using Monte Carlo simulations.

Results: The population typical values of apparent clearance (CL/F) and apparent volume of distribution (V/F) of nirmatrelvir were 2.26 L/h and 15.3 L, respectively. Notably, creatinine clearance (CrCL) significantly influenced the PK variation of nirmatrelvir. Monte Carlo simulations suggested that patients with mild-to-moderate renal impairment experienced a 22.0-59.9% increase in the area under the curve (AUC) when they were administered a standard dose of nirmatrelvir compared to those with normal renal function. The AUC in patients with severe renal impairment after administration of 150 mg q12h nirmatrelvir was similar to that in patients with normal renal function after administration of 300 mg q12h nirmatrelvir.

Conclusions: PPK modeling and simulation provided a reference for the rational clinical application of nirmatrelvir/ritonavir in critically ill Chinese patients.

研究背景本研究旨在建立中国2019年冠状病毒病(COVID-19)感染重症患者中尼马瑞韦/利托那韦的群体药代动力学(PPK)模型,探讨影响尼马瑞韦/利托那韦药代动力学(PK)的因素:方法:共收集了152名患者的285份血清样本和临床数据。采用非线性混合效应模型(NONMEM)方法分析了那瑞瑞韦/利托那韦的药代动力学(PK)模型。通过蒙特卡洛模拟确定了不同肾功能患者的最佳给药方案:结果:nirmatrelvir 的表观清除率(CL/F)和表观分布容积(V/F)的人群典型值分别为 2.26 L/h 和 15.3 L。值得注意的是,肌酐清除率(CrCL)对尼尔马特韦的 PK 变化有显著影响。蒙特卡洛模拟显示,与肾功能正常的患者相比,轻度至中度肾功能受损的患者在服用标准剂量的尼尔马特韦时,其曲线下面积(AUC)会增加 22.0-59.9%。严重肾功能损害患者服用150毫克 q12小时的尼尔马特雷韦后,其AUC与肾功能正常患者服用300毫克 q12小时的尼尔马特雷韦后的AUC相似:PPK建模和模拟为尼马瑞韦/利托那韦在中国重症患者中的临床合理应用提供了参考。
{"title":"Population pharmacokinetics of nirmatrelvir/ritonavir in critically ill Chinese COVID-19 patients and recommendations for medication use: a two-center retrospective study.","authors":"Junjun Xu, Jinmeng Li, Meng Chen, Huifang Jiang, Xudong Fan, Yangmin Hu, Haili Shan, Mingdong Yang, Yichao Xu, Yuying Lang, Haibin Dai, Xinjun Cai","doi":"10.1080/17512433.2024.2410385","DOIUrl":"10.1080/17512433.2024.2410385","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to establish population pharmacokinetics (PPK) models of nirmatrelvir/ritonavir in critically ill Chinese patients with the coronavirus disease 2019 (COVID-19) infection, explore factors affecting the pharmacokinetics (PK) of nirmatrelvir/ritonavir.</p><p><strong>Methods: </strong>A total of 285 serum samples and clinical data were collected from 152 patients. The PPK models of nirmatrelvir/ritonavir were analyzed using nonlinear mixed-effect modeling (NONMEM) approach. The optimal dosing regimen for patients with different renal function was determined using Monte Carlo simulations.</p><p><strong>Results: </strong>The population typical values of apparent clearance (CL/F) and apparent volume of distribution (V/F) of nirmatrelvir were 2.26 L/h and 15.3 L, respectively. Notably, creatinine clearance (CrCL) significantly influenced the PK variation of nirmatrelvir. Monte Carlo simulations suggested that patients with mild-to-moderate renal impairment experienced a 22.0-59.9% increase in the area under the curve (AUC) when they were administered a standard dose of nirmatrelvir compared to those with normal renal function. The AUC in patients with severe renal impairment after administration of 150 mg q12h nirmatrelvir was similar to that in patients with normal renal function after administration of 300 mg q12h nirmatrelvir.</p><p><strong>Conclusions: </strong>PPK modeling and simulation provided a reference for the rational clinical application of nirmatrelvir/ritonavir in critically ill Chinese patients.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Amylin analogs for the treatment of obesity without diabetes: present and future. 用于治疗无糖尿病肥胖症的淀粉类似物:现状与未来。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-30 DOI: 10.1080/17512433.2024.2409403
Theodoros Panou, Evanthia Gouveri, Djordje S Popovic, Nikolaos Papanas

Introduction: Obesity is a pandemic, linked with increased morbidity including diabetes mellitus (DM) and certain cancer types. Amylin is a major regulatory hormone for satiation and food intake perception in humans. Amylin analogs (pramlintide and cagrilintide) are emerging as promising anti-obesity agents in non-DM subjects.

Areas covered: Pramlintide, the first amylin analog, initially used for the treatment of both type 1 and type 2 DM, has demonstrated weight-lowering action. Clinical trials confirmed a weight loss exceeding 3% in the study period without major untoward effects, which was maintained beyond the follow-up period. Recently, cagrilintide, a long-lasting synthetic amylin analog has been introduced. Cagrilintide has achieved adequate weight loss, reaching even more than 10% of the total weight in early clinical trials. However, adverse gastrointestinal effects, particularly nausea, were more frequent compared with pramlintide. Clinical trials have also confirmed the effectiveness of cagrilintide in comparison with glucagon-like peptide 1 receptor agonists.

Expert opinion: Amylin analogs will certainly enrich the growing therapeutic armamentarium aimed at tackling obesity. The most exciting future research venue could be the development of their combinations with other weight-lowering drugs, especially dual and triple incretin-based co-agonists, thus potentially providing massive weight-loss effects.

导言:肥胖症是一种大流行病,与糖尿病(DM)和某些癌症类型等发病率增加有关。淀粉样蛋白是人体饱腹感和食物摄入感的主要调节激素。淀粉样蛋白类似物(普拉林肽和卡格列林肽)正在非糖尿病患者中成为有前景的抗肥胖药物:普拉林肽是第一种淀粉类似物,最初用于治疗 1 型和 2 型糖尿病,已证明具有降低体重的作用。临床试验证实,在研究期间体重下降超过 3%,且无重大不良反应,随访期后仍能保持。最近,一种长效合成淀粉样蛋白类似物卡格列汀(cagrilintide)问世。在早期临床试验中,卡格列林肽的减重效果很好,甚至达到了总重量的 10%以上。然而,与普拉林肽相比,胃肠道的不良反应,尤其是恶心更为频繁。临床试验还证实,与胰高血糖素样肽 1 受体激动剂相比,卡格列净的疗效更好:专家观点:淀粉类似物必将丰富日益增长的肥胖症治疗手段。未来最令人兴奋的研究方向可能是开发淀粉类似物与其他减重药物的组合,特别是与双重和三重胰高血糖素类联合受体激动剂的组合,从而可能产生巨大的减重效果。
{"title":"Amylin analogs for the treatment of obesity without diabetes: present and future.","authors":"Theodoros Panou, Evanthia Gouveri, Djordje S Popovic, Nikolaos Papanas","doi":"10.1080/17512433.2024.2409403","DOIUrl":"https://doi.org/10.1080/17512433.2024.2409403","url":null,"abstract":"<p><strong>Introduction: </strong>Obesity is a pandemic, linked with increased morbidity including diabetes mellitus (DM) and certain cancer types. Amylin is a major regulatory hormone for satiation and food intake perception in humans. Amylin analogs (pramlintide and cagrilintide) are emerging as promising anti-obesity agents in non-DM subjects.</p><p><strong>Areas covered: </strong>Pramlintide, the first amylin analog, initially used for the treatment of both type 1 and type 2 DM, has demonstrated weight-lowering action. Clinical trials confirmed a weight loss exceeding 3% in the study period without major untoward effects, which was maintained beyond the follow-up period. Recently, cagrilintide, a long-lasting synthetic amylin analog has been introduced. Cagrilintide has achieved adequate weight loss, reaching even more than 10% of the total weight in early clinical trials. However, adverse gastrointestinal effects, particularly nausea, were more frequent compared with pramlintide. Clinical trials have also confirmed the effectiveness of cagrilintide in comparison with glucagon-like peptide 1 receptor agonists.</p><p><strong>Expert opinion: </strong>Amylin analogs will certainly enrich the growing therapeutic armamentarium aimed at tackling obesity. The most exciting future research venue could be the development of their combinations with other weight-lowering drugs, especially dual and triple incretin-based co-agonists, thus potentially providing massive weight-loss effects.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reducing the risk of death - a possible outcome in COPD patients. 降低死亡风险--慢性阻塞性肺病患者的一种可能结果。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-26 DOI: 10.1080/17512433.2024.2408272
Mauro Maniscalco, Luigino Calzetta, Paola Rogliani, Mario Cazzola

Introduction: COPD is a leading cause of global mortality, particularly under-recognized and under-diagnosed. In 2020, it was the sixth leading cause of death in the US and has contributed to 4.72% of all-cause mortality (ACM) according to the Global Burden of Disease Study 2017. Factors influencing COPD-related mortality include smoking, aging populations, comorbidities, sarcopenia, physical capacity, and lack of effective treatments.

Areas covered: This review discusses various factors influencing COPD-related mortality and analyzes observational studies and pivotal RCTs evaluating the impact of different therapies on ACM.

Expert opinion: COPD significantly impacts ACM, necessitating effective management strategies. Smoking cessation is crucial in reducing mortality risk. Exacerbation management and comorbidity treatment are essential to improve patient outcomes. Various therapeutic interventions, such as smoking cessation, vaccination, long-term oxygen therapy, and lung volume reduction surgery, have shown benefits in reducing mortality. Pharmacotherapies might reduce the risk of mortality, although the current scientific evidences remain inconclusive. Advances in pharmacological interventions, tailored treatment plans, and physical activity programs are vital. More robust and long-term studies, focusing on real-world data and addressing biases in treatment allocation, are needed to conclusively determine the efficacy of different therapies in reducing ACM in COPD patients.

导言:慢性阻塞性肺病是导致全球死亡的主要原因,尤其是认识不足和诊断不足。根据《2017 年全球疾病负担研究》,2020 年慢性阻塞性肺病是美国第六大死因,占全因死亡率(ACM)的 4.72%。影响慢性阻塞性肺疾病相关死亡率的因素包括吸烟、人口老龄化、合并症、肌肉疏松症、体能以及缺乏有效的治疗方法:本综述讨论了影响慢性阻塞性肺病相关死亡率的各种因素,并分析了评估不同疗法对ACM影响的观察性研究和关键RCT:专家观点:慢性阻塞性肺病对急性心肌梗死有重大影响,因此必须采取有效的管理策略。戒烟对降低死亡风险至关重要。病情加重管理和合并症治疗对改善患者预后至关重要。各种治疗干预措施,如戒烟、疫苗接种、长期氧疗和肺容积缩小手术,都显示出降低死亡率的益处。药物治疗可降低死亡风险,但目前的科学证据仍不确定。药物干预、量身定制的治疗计划和体育锻炼计划的进步至关重要。要想最终确定不同疗法在减少慢性阻塞性肺疾病患者 ACM 方面的疗效,还需要开展更多稳健而长期的研究,重点关注真实世界的数据,并解决治疗分配中的偏差问题。
{"title":"Reducing the risk of death - a possible outcome in COPD patients.","authors":"Mauro Maniscalco, Luigino Calzetta, Paola Rogliani, Mario Cazzola","doi":"10.1080/17512433.2024.2408272","DOIUrl":"10.1080/17512433.2024.2408272","url":null,"abstract":"<p><strong>Introduction: </strong>COPD is a leading cause of global mortality, particularly under-recognized and under-diagnosed. In 2020, it was the sixth leading cause of death in the US and has contributed to 4.72% of all-cause mortality (ACM) according to the Global Burden of Disease Study 2017. Factors influencing COPD-related mortality include smoking, aging populations, comorbidities, sarcopenia, physical capacity, and lack of effective treatments.</p><p><strong>Areas covered: </strong>This review discusses various factors influencing COPD-related mortality and analyzes observational studies and pivotal RCTs evaluating the impact of different therapies on ACM.</p><p><strong>Expert opinion: </strong>COPD significantly impacts ACM, necessitating effective management strategies. Smoking cessation is crucial in reducing mortality risk. Exacerbation management and comorbidity treatment are essential to improve patient outcomes. Various therapeutic interventions, such as smoking cessation, vaccination, long-term oxygen therapy, and lung volume reduction surgery, have shown benefits in reducing mortality. Pharmacotherapies might reduce the risk of mortality, although the current scientific evidences remain inconclusive. Advances in pharmacological interventions, tailored treatment plans, and physical activity programs are vital. More robust and long-term studies, focusing on real-world data and addressing biases in treatment allocation, are needed to conclusively determine the efficacy of different therapies in reducing ACM in COPD patients.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Is therapeutic drug monitoring a dancing partner for TNF-α inhibitors in real-world practice? Answers from an updated systematic review and meta-analysis. 治疗药物监测是 TNF-α 抑制剂在实际应用中的舞伴吗?最新系统综述和荟萃分析给出的答案。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-21 DOI: 10.1080/17512433.2024.2403641
Yang Hu, Zaiwei Song, Yuan Gao, Dan Jiang, Yiwen Ran, Yi Ma, Huibo Li, Rongsheng Zhao

Introduction: This systematic review aimed to determine the effect of therapeutic drug monitoring (TDM) for tumor necrosis factor-α inhibitors (TNF-αI) in immune-mediated inflammatory diseases (IMIDs) based on real-world evidence, as results from published meta-analyses based on randomized controlled trials (RCTs) may not fully capture the nuances of clinical practice due to strict criteria.

Methods: We searched PubMed, Embase, and the Cochrane Library up to 1 August 2023. Cohort studies comparing TDM (proactive and reactive) with empirical management were included. Primary outcome was effectiveness [for IBDs: clinical remission; for rheumatic diseases: clinical remission or low disease activity], with certainty of evidence appraised using the GRADE approach. Secondary outcomes included treatment failure, serious adverse events (SAEs), IMIDs-related surgeries or hospitalizations, and anti-drug antibodies (ADAs) development risk.

Results: Twenty-four cohort studies were included and almost all were on infliximab. For IBDs, compared with empirical management, proactive TDM significantly improved clinical remission (RR = 1.15, 95% CI = 1.04-1.28), reduced IBDs-related surgeries (RR = 0.46, 95% CI = 0.26-0.81), hospitalizations (RR = 0.60, 95% CI = 0.43-0.83), SAEs (RR = 0.23, 95% CI = 0.07-0.76), and ADAs development risk (RR = 0.34, 95% CI = 0.19-0.60). Reactive TDM significantly lowered hospitalization rates and might be cost-effective. Proactive TDM outperformed reactive TDM in secondary outcomes. For rheumatic diseases, benefits of TDM were inconclusive due to limited evidence.

Conclusions: Real-world evidence supports proactive TDM of TNF-αI (particularly infliximab) in IBDs to improve effectiveness, safety, and immunogenicity. However, benefits of TDM for different TNF-αI in other IMIDs remain uncertain.

Protocol registration: www.crd.york.ac.uk/ PROSPERO identifier is CRD42022370846.

导言:由于基于随机对照试验(RCT)的已发表荟萃分析的结果可能因严格的标准而无法完全反映临床实践的细微差别,因此本系统综述旨在根据现实世界的证据确定肿瘤坏死因子-α抑制剂(TNF-αI)治疗药物监测(TDM)在免疫介导的炎症性疾病(IMIDs)中的效果:我们检索了截至 2023 年 8 月 1 日的 PubMed、Embase 和 Cochrane 图书馆。方法:我们检索了截至 2023 年 8 月 1 日的 PubM、Embase 和 Cochrane 图书馆,纳入了比较 TDM(主动和被动)与经验性管理的队列研究。主要结果为有效性[对于IBD:临床缓解;对于风湿性疾病:临床缓解或低疾病活动性],采用GRADE方法评估证据的确定性。次要结果包括治疗失败、严重不良事件(SAEs)、IMIDs相关手术或住院以及抗药抗体(ADAs)发展风险:结果:共纳入了 24 项队列研究,几乎所有研究都涉及英夫利西单抗。对于 IBDs,与经验性治疗相比,主动性 TDM 可显著改善临床缓解(RR = 1.15,95% CI = 1.04-1.28),减少 IBDs 相关手术(RR = 0.46,95% CI = 0.26-0.81)、住院(RR = 0.60,95% CI = 0.43-0.83)、SAEs(RR = 0.23,95% CI = 0.07-0.76)和 ADAs 发展风险(RR = 0.34,95% CI = 0.19-0.60)。反应性 TDM 能明显降低住院率,可能具有成本效益。在次要结果方面,主动式TDM优于被动式TDM。对于风湿性疾病,由于证据有限,TDM的益处尚无定论:真实世界的证据支持对IBD患者的TNF-αI(尤其是英夫利西单抗)进行主动TDM,以提高有效性、安全性和免疫原性。然而,TDM对其他IMIDs中不同TNF-αI的益处仍不确定。协议注册:www.crd.york.ac.uk/ PROSPERO标识符为CRD42022370846。
{"title":"Is therapeutic drug monitoring a dancing partner for TNF-α inhibitors in real-world practice? Answers from an updated systematic review and meta-analysis.","authors":"Yang Hu, Zaiwei Song, Yuan Gao, Dan Jiang, Yiwen Ran, Yi Ma, Huibo Li, Rongsheng Zhao","doi":"10.1080/17512433.2024.2403641","DOIUrl":"10.1080/17512433.2024.2403641","url":null,"abstract":"<p><strong>Introduction: </strong>This systematic review aimed to determine the effect of therapeutic drug monitoring (TDM) for tumor necrosis factor-α inhibitors (TNF-αI) in immune-mediated inflammatory diseases (IMIDs) based on real-world evidence, as results from published meta-analyses based on randomized controlled trials (RCTs) may not fully capture the nuances of clinical practice due to strict criteria.</p><p><strong>Methods: </strong>We searched PubMed, Embase, and the Cochrane Library up to 1 August 2023. Cohort studies comparing TDM (proactive and reactive) with empirical management were included. Primary outcome was effectiveness [for IBDs: clinical remission; for rheumatic diseases: clinical remission or low disease activity], with certainty of evidence appraised using the GRADE approach. Secondary outcomes included treatment failure, serious adverse events (SAEs), IMIDs-related surgeries or hospitalizations, and anti-drug antibodies (ADAs) development risk.</p><p><strong>Results: </strong>Twenty-four cohort studies were included and almost all were on infliximab. For IBDs, compared with empirical management, proactive TDM significantly improved clinical remission (RR = 1.15, 95% CI = 1.04-1.28), reduced IBDs-related surgeries (RR = 0.46, 95% CI = 0.26-0.81), hospitalizations (RR = 0.60, 95% CI = 0.43-0.83), SAEs (RR = 0.23, 95% CI = 0.07-0.76), and ADAs development risk (RR = 0.34, 95% CI = 0.19-0.60). Reactive TDM significantly lowered hospitalization rates and might be cost-effective. Proactive TDM outperformed reactive TDM in secondary outcomes. For rheumatic diseases, benefits of TDM were inconclusive due to limited evidence.</p><p><strong>Conclusions: </strong>Real-world evidence supports proactive TDM of TNF-αI (particularly infliximab) in IBDs to improve effectiveness, safety, and immunogenicity. However, benefits of TDM for different TNF-αI in other IMIDs remain uncertain.</p><p><strong>Protocol registration: </strong>www.crd.york.ac.uk/ PROSPERO identifier is CRD42022370846.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of fasudil on clinical outcomes of pulmonary hypertension: a systematic review and meta-analysis. 法舒地尔对肺动脉高压临床疗效的影响:系统综述和荟萃分析。
IF 4.4 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-13 DOI: 10.1080/17512433.2024.2404688
Wanying Bao,Mengxin Cheng,Xiaoye Chen,Tao Wang,Dan Xu,Hualin Liao,Lei Chen,Fuqiang Wen,Junyun He,Jun Chen
BACKGROUNDPulmonary hypertension (PH) is a life-threatening condition with high mortality, categorized into 5 Groups based on distinct etiologies. Fasudil, a potent vasodilator targeting the RhoA/Rho kinase pathway, holds promise for diverse PH pathologies. However, a comprehensive systematic evaluation of its clinical benefits remains elusive.METHODSWe conducted a systematic search across several databases. Meta-analysis using odds ratio and mean difference was performed, with an assessment of studies' quality and pooled evidence.RESULTSStudies on Group-2 and -3 PH reports eligible data for meta-analysis. Inclusion of 3269 patients with Group-3 PH demonstrated that fasudil significantly increased effective events, FEV1, 6-minute walking distance (6MWD) and arterial PaO2, and decreased mean pulmonary artery pressure (mPAP) and pulmonary artery systolic pressure (PASP); Inclusion of 197 patients with Group-2 PH suggested that fasudil significantly increased 6MWD and PaO2, and decreased PASP. Subgroup analysis revealed no significant difference between dosages of 30 and 60 mg/day, while durations and methods of fasudil administration might affect therapeutic effectiveness in patients with Group-3 PH.CONCLUSIONSBy providing comprehensive and robust evidence, our study favor the beneficial effects of fasudil by enhancing FEV1, 6MWD and PaO2, and reducing mPAP and PASP on patients with Group-3 PH, suggesting fasudil as a viable treatment recommendation for these patients and highlighting the need for further studies to inform healthcare policies.PROTOCOL REGISTRATIONwww.crd.york.ac.uk/prospero identifier is CRD42022308947.
背景肺动脉高压(PH)是一种威胁生命的疾病,死亡率很高,根据不同的病因可分为 5 类。法舒地尔是一种靶向 RhoA/Rho 激酶通路的强效血管扩张剂,有望治疗各种 PH 病症。方法我们在多个数据库中进行了系统性检索。结果关于第 2 组和第 3 组 PH 的研究报告符合荟萃分析的数据要求。纳入3269例3组PH患者的研究表明,法舒地尔能显著增加有效事件、FEV1、6分钟步行距离(6MWD)和动脉PaO2,降低平均肺动脉压(mPAP)和肺动脉收缩压(PASP);纳入197例2组PH患者的研究表明,法舒地尔能显著增加6MWD和PaO2,降低PASP。亚组分析显示,30 毫克/天和 60 毫克/天的剂量之间没有明显差异,而法舒地尔的用药时间和方法可能会影响第 3 组 PH 患者的疗效。结论通过提供全面而有力的证据,我们的研究支持法舒地尔通过提高FEV1、6MWD和PaO2,降低mPAP和PASP对3组PH患者的有益作用,建议将法舒地尔作为这些患者的可行治疗建议,并强调了进一步研究的必要性,以便为医疗保健政策提供信息。PROTOCOL REGISTRATIONwww.crd.york.ac.uk/prospero identifier is CRD42022308947.
{"title":"Effect of fasudil on clinical outcomes of pulmonary hypertension: a systematic review and meta-analysis.","authors":"Wanying Bao,Mengxin Cheng,Xiaoye Chen,Tao Wang,Dan Xu,Hualin Liao,Lei Chen,Fuqiang Wen,Junyun He,Jun Chen","doi":"10.1080/17512433.2024.2404688","DOIUrl":"https://doi.org/10.1080/17512433.2024.2404688","url":null,"abstract":"BACKGROUNDPulmonary hypertension (PH) is a life-threatening condition with high mortality, categorized into 5 Groups based on distinct etiologies. Fasudil, a potent vasodilator targeting the RhoA/Rho kinase pathway, holds promise for diverse PH pathologies. However, a comprehensive systematic evaluation of its clinical benefits remains elusive.METHODSWe conducted a systematic search across several databases. Meta-analysis using odds ratio and mean difference was performed, with an assessment of studies' quality and pooled evidence.RESULTSStudies on Group-2 and -3 PH reports eligible data for meta-analysis. Inclusion of 3269 patients with Group-3 PH demonstrated that fasudil significantly increased effective events, FEV1, 6-minute walking distance (6MWD) and arterial PaO2, and decreased mean pulmonary artery pressure (mPAP) and pulmonary artery systolic pressure (PASP); Inclusion of 197 patients with Group-2 PH suggested that fasudil significantly increased 6MWD and PaO2, and decreased PASP. Subgroup analysis revealed no significant difference between dosages of 30 and 60 mg/day, while durations and methods of fasudil administration might affect therapeutic effectiveness in patients with Group-3 PH.CONCLUSIONSBy providing comprehensive and robust evidence, our study favor the beneficial effects of fasudil by enhancing FEV1, 6MWD and PaO2, and reducing mPAP and PASP on patients with Group-3 PH, suggesting fasudil as a viable treatment recommendation for these patients and highlighting the need for further studies to inform healthcare policies.PROTOCOL REGISTRATIONwww.crd.york.ac.uk/prospero identifier is CRD42022308947.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analyzing the clinical efficacy and safety of levocetirizine based on its receptor occupancy, intraclass comparison and role in the treatment of CSU: an AROG consensus statement. 根据左西替利嗪的受体占据率、类内比较和在 CSU 治疗中的作用分析其临床疗效和安全性:AROG 共识声明。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-12 DOI: 10.1080/17512433.2024.2401093
Kabir Sardana, C R Srinivasan, Mukesh Girdhar, Neirita Hazarika, Krina Patel, Narayan Rao, Akshay Jain, Jaspriya Sandhu, Shivani Bansal, Sunil Ghate, Rizwan Haq, Dhruv Premy Agarwal

Introduction: Chronic spontaneous urticaria (CSU) is characterized by urticaria persisting for more than 6 weeks. Antihistamines, notably sgAH (second generation antihistamines) are the first line of treatment for CSU.

Areas covered: This consensus aimed to review the existing research on receptor occupancy of antihistamines, including levocetirizine, and translate its implications in the treatment of CSU. The consensus deliberations were under the banner of the Antihistamine Receptor Occupancy Group (AROG) from India, an expert panel of 12 dermatologists with a mix of institutional and practitioner backgrounds. This group analyzed the existing translational research on the receptor occupancy of levocetirizine to establish the clinical efficacy and safety of levocetirizine in the treatment of CSU using the grading of recommendations assessment, development, and evaluation (GRADE) method vis-a-vis the varied SGAH.

Expert opinion: SGAH constitute the first step in the therapeutic ladder for managing CSU. Levocetirizine has high bioavailability, high affinity and occupancy of the H1 receptor, rapid onset of action, limited distribution and minimal hepatic metabolism. It exhibits significant anti-inflammatory effects at clinically relevant concentrations. The marked receptor occupancy translates to enhanced efficacy as compared to similarly dosed SGAH with the lower cost making it an appropriate drug for chronic use. Receptor occupancy should be the basis of intra-class head-to-head trials in CSU.

导言:慢性自发性荨麻疹(CSU)的特征是荨麻疹持续6周以上,并导致严重的发病率。抗组胺药,尤其是第二代抗组胺药(sgAH)是治疗 CSU 的一线药物:本共识旨在回顾有关抗组胺药(包括左西替利嗪)受体占用的现有转化研究,并确定其在 CSU 治疗中的作用。该共识由来自印度的抗组胺药受体占位小组(AROG)牵头,该小组由来自不同地区的十二名皮肤科专家组成,他们具有不同的机构和从业背景。该共识分析了现有关于左西替利嗪受体占位的转化研究,采用建议评估、开发和评价分级(GRADE)方法,与不同的SGAH.专家意见相比,确定了左西替利嗪治疗CSU的临床疗效和安全性:第二代抗组胺药是治疗CSU的第一步。左西替利嗪的生物利用度高,对H1受体的亲和力和占据率高,起效迅速,分布有限,肝脏代谢极少。在临床相关浓度下,它具有明显的抗炎作用。与类似剂量的 SGAH 相比,其明显的受体占有率可转化为更好的疗效,而且分子成本较低,适合长期使用。受体占用率应作为 CSU 类内头对头试验的基础。
{"title":"Analyzing the clinical efficacy and safety of levocetirizine based on its receptor occupancy, intraclass comparison and role in the treatment of CSU: an AROG consensus statement.","authors":"Kabir Sardana, C R Srinivasan, Mukesh Girdhar, Neirita Hazarika, Krina Patel, Narayan Rao, Akshay Jain, Jaspriya Sandhu, Shivani Bansal, Sunil Ghate, Rizwan Haq, Dhruv Premy Agarwal","doi":"10.1080/17512433.2024.2401093","DOIUrl":"10.1080/17512433.2024.2401093","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic spontaneous urticaria (CSU) is characterized by urticaria persisting for more than 6 weeks. Antihistamines, notably sgAH (second generation antihistamines) are the first line of treatment for CSU.</p><p><strong>Areas covered: </strong>This consensus aimed to review the existing research on receptor occupancy of antihistamines, including levocetirizine, and translate its implications in the treatment of CSU. The consensus deliberations were under the banner of the Antihistamine Receptor Occupancy Group (AROG) from India, an expert panel of 12 dermatologists with a mix of institutional and practitioner backgrounds. This group analyzed the existing translational research on the receptor occupancy of levocetirizine to establish the clinical efficacy and safety of levocetirizine in the treatment of CSU using the grading of recommendations assessment, development, and evaluation (GRADE) method vis-a-vis the varied SGAH.</p><p><strong>Expert opinion: </strong>SGAH constitute the first step in the therapeutic ladder for managing CSU. Levocetirizine has high bioavailability, high affinity and occupancy of the H1 receptor, rapid onset of action, limited distribution and minimal hepatic metabolism. It exhibits significant anti-inflammatory effects at clinically relevant concentrations. The marked receptor occupancy translates to enhanced efficacy as compared to similarly dosed SGAH with the lower cost making it an appropriate drug for chronic use. Receptor occupancy should be the basis of intra-class head-to-head trials in CSU.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Expert Review of Clinical Pharmacology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1