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Diagnosis and Management of Parathyroid Carcinoma. 甲状旁腺癌的诊断和治疗。
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-05 DOI: 10.1002/cpt.3432
Alexander Lazzaro, Grace Qing Zhao, Matthew Kulke

Parathyroid carcinoma (PC) is a rare malignancy, often characterized by the unregulated secretion of parathyroid hormone. The sequelae of severe hypercalcemia together with direct complications from tumor dissemination in patients with advanced disease are usually fatal. Due to its rarity, formal studies to guide the diagnosis and management of parathyroid carcinoma are lacking. However, recent data from case reports, case series, and registry studies suggest the emergence of new and effective treatment approaches for this understudied disease. We reviewed existing literature on the diagnosis and management of parathyroid carcinoma. Our findings suggest that traditional approaches such as surgical resection for both localized and metastatic diseases continue to play an important role in patient management. For patients with unresectable disease, newer systemic treatment approaches, including the use of temozolomide and tyrosine kinase inhibitors, may offer clinical benefit.

甲状旁腺癌(PC)是一种罕见的恶性肿瘤,通常以甲状旁腺激素分泌失调为特征。晚期患者通常会因严重的高钙血症以及肿瘤扩散引起的直接并发症而死亡。由于甲状旁腺癌非常罕见,目前还缺乏正式的研究来指导甲状旁腺癌的诊断和治疗。不过,最近来自病例报告、系列病例和登记研究的数据表明,这种研究不足的疾病正在出现新的有效治疗方法。我们回顾了有关甲状旁腺癌诊断和治疗的现有文献。我们的研究结果表明,对局部和转移性疾病进行手术切除等传统方法仍在患者治疗中发挥着重要作用。对于无法切除的患者,包括替莫唑胺和酪氨酸激酶抑制剂在内的新型全身治疗方法可能会带来临床益处。
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引用次数: 0
First-in-Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of BMS-986308: A Renal Outer Medullary Potassium Channel Inhibitor. 评估 BMS-986308:肾外髓质钾通道抑制剂的安全性、药代动力学和药效学的首次人体研究。
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-02 DOI: 10.1002/cpt.3430
Sharif I Soleman, Juan Maya, Paul Levesque, Atif Mohammad, Lisa Christopher, Justin Schumacher, Aparna Nanduri, Pitchumani Sivakumar, Marc Kozinn, Philippe Costet, Chang Wang, Jeremy Richter, Dara Hawthorne, Anh Bui, Veena S Rao, Daniel Dickerson, Jeffrey Testani, Francisco Ramírez-Valle, Frédéric Baribaud, Bindu Murthy, Samira Merali

In patients with heart failure (HF) who respond inadequately to loop diuretic therapy, BMS-986308, an oral, selective, reversible renal outer medullary potassium channel (ROMK) inhibitor may represent an effective diuretic with a novel mechanism of action. We present data from the first-in-human study aimed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) following single ascending doses of BMS-986308 in healthy adult participants. Forty healthy participants, aged from 20 to 55 years, and body mass index (BMI) from 19.8 to 31.6 kg/m2 were assigned to 1 of 5 dose cohorts (1, 3, 10, 30, and 100 mg) and randomized (6:2) to receive BMS-986308 oral solution or matching placebo. Following administration, BMS-986308 was rapidly absorbed with a median time to maximum concentration (Tmax) of 1.00 to 1.75 h and exhibiting a mean terminal half-life (t1/2) of approximately 13 h. Dose proportionality was evident in BMS-986308 area under the concentration-time curve (AUC), while maximum concentration (Cmax) was slightly greater than dose-proportional. We observed that urine output (or diuresis; mL) and urinary sodium excretion (or natriuresis; mmol) increased in a dose-dependent manner, starting at a minimum pharmacologically active dose of 30 mg. The largest mean changes from baseline in diuresis and natriuresis occurred in both the 6- and -24 h post-dose period following administration of 100 mg (1683.0 mL and 2055.3 mL, and 231.7 mmol and 213.7 mmol, respectively; ***P < 0.001). Overall, single-dose BMS-986308 was found to be safe, well-tolerated, with an excellent PK profile, and substantial diuretic and natriuretic activity.

对于襻利尿剂治疗效果不佳的心力衰竭(HF)患者,BMS-986308--一种口服、选择性、可逆的肾外髓钾通道(ROMK)抑制剂--可能是一种具有新型作用机制的有效利尿剂。我们展示了首次人体研究的数据,该研究旨在评估健康成人服用单次升剂量 BMS-986308 后的安全性、耐受性、药代动力学 (PK) 和药效学 (PD)。研究人员将 40 名年龄介于 20 至 55 岁之间、体重指数(BMI)介于 19.8 至 31.6 kg/m2 之间的健康参与者分配到 5 个剂量组(1、3、10、30 和 100 毫克)中的一个,并随机(6:2)接受 BMS-986308 口服液或匹配的安慰剂。给药后,BMS-986308吸收迅速,达到最大浓度(Tmax)的中位时间为1.00至1.75小时,平均终末半衰期(t1/2)约为13小时。BMS-986308的浓度-时间曲线下面积(AUC)明显呈剂量比例关系,而最大浓度(Cmax)略高于剂量比例关系。我们观察到,从最低药理活性剂量 30 毫克开始,尿量(或利尿;毫升)和尿钠排泄量(或利尿;毫摩尔)的增加呈剂量依赖性。在服用 100 毫克后的 6 小时和 24 小时内,尿量和钠排泄量与基线相比的平均变化最大(分别为 1683.0 毫升和 2055.3 毫升,以及 231.7 毫摩尔和 213.7 毫摩尔;***P
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引用次数: 0
Assessing Post-Marketing Requirements for Orphan Drugs: A Cross-Sectional Analysis of FDA and EMA Oversight. 评估孤儿药上市后的要求:对 FDA 和 EMA 监督的横向分析。
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-28 DOI: 10.1002/cpt.3397
Jae Hyeon Yu, Sangwon Lee, Yoon Jung Kim, Won Young Kim, Min Jung Lee, Yun Kim

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) oversee pharmaceutical regulations, including orphan drugs targeting rare diseases with limited patient populations. Post-marketing studies are crucial for monitoring safety and efficacy, with post-marketing requirements (PMRs) mandated by the regulatory agencies to ensure compliance. This study aims to compare PMR statuses, objectives, and pivotal trial characteristics of orphan drugs approved by the FDA (n = 154) and EMA (n = 79) from 2008 to 2018, shedding light on regulatory differences and their impact on drug development. Contrary to expectations, our analysis found no significant disparity in the proportion of orphan drugs with and without PMRs approved by both the FDA (48.1%) and EMA (55.7%). Safety concerns surrounding orphan drugs post-approval, attributed partly to pivotal trial design, underscore the need for robust post-marketing surveillance. While the FDA primarily focuses on post-marketing safety (36.1%), the EMA places a higher emphasis on both efficacy and safety (47.1%), reflecting distinct approaches to PMR management between the two regulatory bodies. The observed trend of delayed PMRs at the EMA (47.1%) highlights the importance of effective cooperation between regulators and pharmaceutical companies to ensure the timely completion of PMRs and enhance drug safety.

美国食品和药物管理局 (FDA) 和欧洲药品管理局 (EMA) 负责监管药品法规,包括针对患者人数有限的罕见病的孤儿药。上市后研究对于监测安全性和有效性至关重要,监管机构规定了上市后要求 (PMR),以确保合规性。本研究旨在比较 2008 年至 2018 年期间 FDA(n = 154)和 EMA(n = 79)批准的孤儿药的 PMR 状态、目标和关键试验特征,揭示监管差异及其对药物开发的影响。与预期相反,我们的分析发现,FDA(48.1%)和 EMA(55.7%)批准的孤儿药中有 PMR 和无 PMR 的比例并无明显差异。孤儿药批准后的安全性问题部分归因于关键性试验的设计,这凸显了上市后严格监控的必要性。FDA 主要关注上市后的安全性(36.1%),而 EMA 则更重视疗效和安全性(47.1%),这反映了两个监管机构在 PMR 管理方面的不同方法。观察到的 EMA PMR 延误趋势(47.1%)突出了监管机构与制药公司之间有效合作的重要性,以确保及时完成 PMR 并提高药物安全性。
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引用次数: 0
A Pooled Population Pharmacokinetic Study of Oral and Intravenous Administration of Clavulanic Acid in Neonates and Infants: Targeting Effective Beta-Lactamase Inhibition. 新生儿和婴儿口服和静脉注射克拉维酸的人群药代动力学研究:以有效抑制β-内酰胺酶为目标。
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-28 DOI: 10.1002/cpt.3423
Stef Schouwenburg, Fleur M Keij, Gerdien A Tramper-Stranders, René F Kornelisse, Irwin K M Reiss, Pieter A J G de Cock, Evelyn Dhont, Kevin M Watt, Anouk E Muller, Robert B Flint, Birgit C P Koch, Karel Allegaert, Tim Preijers

Data published on the oral clavulanic acid pharmacokinetics in the pediatric population is lacking. This research aimed to describe clavulanic acid disposition following oral and intravenous administration and to provide insights into clavulanic acid exposure based on threshold concentrations for (pre-)term neonates and infants. This pooled population pharmacokinetic study combined four datasets for analysis in NONMEM v7.4.3. Clavulanic acid exposure was simulated using the percentage of time above the threshold concentrations (%fT > CT). Multiple dosage regimens and amoxicillin/clavulanic acid dosage ratios were evaluated. The cohort consisted of 89 (42 oral, 47 intravenous) subjects (403 samples) with a median (range) postnatal age 54.5 days (0-365), gestational age 37.4 weeks (23.0-41.7), and current bodyweight 3.9 kg (0.6-9.0). A one-compartment model with first-order absorption best described clavulanic acid pharmacokinetics with postnatal age as a covariate on the inter-individual variability of clearance. Oral bioavailability was 24.4% in neonates up to 10 days of age. An oral dosing regimen 90 mg/kg/day amoxicillin/clavulanic acid (4:1 ratio) resulted in 40.2% of simulated patients achieving 100% fT > CT,2mg/L. An amoxicillin/clavulanic acid ratio of 4:1 is preferred for neonatal oral regimens due to the higher exposure along the entire %fT > CT range (0-100%) as ratios higher than 4:1 might result in inadequate exposure. Our results highlight substantial exposure differences (%fT > CT) when using threshold concentrations of 1 mg/L vs. 2 mg/L. This first population pharmacokinetic model for clavulanic acid in neonates may serve as a foundational step for future research, once more precise clavulanic acid targets become available.

目前还缺乏有关儿童口服克拉维酸药代动力学的数据。本研究旨在描述克拉维酸在口服和静脉给药后的处置,并根据(足月前)新生儿和婴儿的阈值浓度提供克拉维酸暴露的见解。这项集合人群药代动力学研究结合了四个数据集,使用 NONMEM v7.4.3 进行分析。使用高于阈值浓度的时间百分比(%fT > CT)模拟克拉维酸暴露。对多种给药方案和阿莫西林/克拉维酸剂量比进行了评估。组群包括 89 名受试者(42 名口服,47 名静脉注射)(403 个样本),中位(范围)产后年龄为 54.5 天(0-365 天),胎龄为 37.4 周(23.0-41.7 周),当前体重为 3.9 千克(0.6-9.0 千克)。一阶吸收的单室模型最能描述克拉维酸的药代动力学,产后年龄是影响清除率个体间变化的协变量。10 天以内的新生儿口服生物利用度为 24.4%。阿莫西林/克拉维酸口服剂量为 90 毫克/千克/天(4:1 比例),40.2% 的模拟患者的 fT 100%>CT,2毫克/升。新生儿口服药物的阿莫西林/克拉维酸比例最好为 4:1,因为在整个 fT > CT 百分比范围(0-100%)内的暴露量较高,而比例高于 4:1 可能会导致暴露量不足。我们的研究结果表明,当使用 1 mg/L 与 2 mg/L 的阈值浓度时,暴露量(%fT > CT)存在很大差异。一旦有了更精确的克拉维酸目标值,这个新生儿体内克拉维酸的首个群体药代动力学模型可作为未来研究的基础步骤。
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引用次数: 0
The Rare Disease Moonshot: Paradigms Shift, Translational Medicine, and Regulatory Science for the World's Rarest Conditions. 罕见病大跃进:世界罕见疾病的范式转变、转化医学和监管科学。
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-23 DOI: 10.1002/cpt.3428
Cécile Ollivier, Solange Corriol-Rohou, Marta Del Álamo, Roseline Favresse, Johanna Kostenzer, Mathieu Boudes, Anton E Ussi, Klaus Viel, R Michael Linden, Magda Chlebus
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引用次数: 0
Development of a Multifaceted Program for Pharmacogenetics Adoption at an Academic Medical Center: Practical Considerations and Lessons Learned 在学术医学中心制定药物遗传学应用的多方面计划:实际考虑因素与经验教训。
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-21 DOI: 10.1002/cpt.3402
Tyler Shugg, Emma M. Tillman, Amy M. Breman, Jennelle C. Hodge, Christine A. McDonald, Reynold C. Ly, Elizabeth J. Rowe, Wilberforce Osei, Tayler B. Smith, Peter H. Schwartz, John T. Callaghan, Victoria M. Pratt, Sheryl Lynch, Michael T. Eadon, Todd C. Skaar

In 2019, Indiana University launched the Precision Health Initiative to enhance the institutional adoption of precision medicine, including pharmacogenetics (PGx) implementation, at university-affiliated practice sites across Indiana. The overarching goal of this PGx implementation program was to facilitate the sustainable adoption of genotype-guided prescribing into routine clinical care. To accomplish this goal, we pursued the following specific objectives: (i) to integrate PGx testing into existing healthcare system processes; (ii) to implement drug–gene pairs with high-level evidence and educate providers and pharmacists on established clinical management recommendations; (iii) to engage key stakeholders, including patients to optimize the return of results for PGx testing; (iv) to reduce health disparities through the targeted inclusion of underrepresented populations; (v) and to track third-party reimbursement. This tutorial details our multifaceted PGx implementation program, including descriptions of our interventions, the critical challenges faced, and the major program successes. By describing our experience, we aim to assist other clinical teams in achieving sustainable PGx implementation in their health systems.

2019 年,印第安纳大学发起了 "精准健康倡议",以加强精准医疗的机构采用,包括在印第安纳州各大学附属实践点实施药物遗传学 (PGx)。该 PGx 实施计划的总体目标是促进基因型指导处方在常规临床护理中的可持续应用。为实现这一目标,我们努力实现以下具体目标:(i) 将 PGx 检测纳入现有的医疗保健系统流程;(ii) 实施具有高水平证据的药物基因配对,并就既定的临床管理建议对医疗服务提供者和药剂师进行教育;(iii) 让包括患者在内的主要利益相关者参与进来,以优化 PGx 检测结果的回报;(iv) 通过有针对性地纳入代表性不足的人群来减少健康差异;(v) 跟踪第三方报销情况。本教程详细介绍了我们多方面的 PGx 实施计划,包括我们的干预措施、面临的关键挑战和计划的主要成功之处。通过介绍我们的经验,我们旨在帮助其他临床团队在其医疗系统中实现可持续的 PGx 实施。
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引用次数: 0
Progress in Pharmacometrics Implementation and Regulatory Integration in Africa: A Systematic Review. 非洲药物计量学实施和监管一体化的进展:系统回顾。
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-20 DOI: 10.1002/cpt.3415
Bonginkosi S'fiso Ndzamba, Samuel Egieyeh, Pius Fasinu

The availability of clinical trial data, advocacy, and increased funding has facilitated the implementation of pharmacometrics in Africa, resulting in the establishment of additional training programs for pharmacometricians. This study conducted a systematic review to evaluate the progress made from the implementation of pharmacometrics in clinical drug development and its adoption into drug approval by regulatory authorities in Africa. We performed a comprehensive literature search using major databases such as PubMed and Google Scholar. The study included articles published until 2024, with no lower cutoff. Articles were excluded if not addressing the research question or of pharmacometrics studies done outside Africa with no collaboration with African researchers (study setting). For the review, a total of 121 articles were included for analysis. Among the reported pharmacometrics approaches, Population pharmacokinetics modeling approaches are the most used (95 (78.5%)). South Africa and Uganda researchers have the most research output in pharmacometrics in Africa (82 (89.1%) and 7 (7.61%), respectively), with the University of Cape Town (South Africa) producing the highest (71 (78.8%)) of all article in Africa. The most studied conditions are TB (43 (35.5%)), HIV (33 (27.3%), TB and HIV (22 (18.2%)), and malaria (12 (9.92%). Pharmacometrics is gaining momentum in Africa, and the progress made since inception will significantly improve the safety and efficacy of therapeutic agents used to treat HIV, TB, and other emerging conditions.

临床试验数据的可获得性、宣传和资金的增加促进了药物计量学在非洲的实施,从而建立了更多的药物计量学培训计划。本研究进行了一次系统性回顾,以评估药物计量学在临床药物开发中的应用进展,以及非洲监管机构在药物审批中采用药物计量学的情况。我们使用 PubMed 和谷歌学术等主要数据库进行了全面的文献检索。研究包括 2024 年之前发表的文章,不设下限。不涉及研究问题的文章或在非洲以外进行的、未与非洲研究人员合作的药物计量学研究(研究环境)的文章将被排除在外。本次综述共纳入 121 篇文章进行分析。在报告的药物计量学方法中,人口药代动力学建模方法使用最多(95 篇(78.5%))。南非和乌干达研究人员的药物计量学研究成果最多(分别为 82 (89.1%) 和 7 (7.61%)),其中开普敦大学(南非)的研究成果最多(71 (78.8%))。研究最多的疾病是肺结核(43(35.5%))、艾滋病(33(27.3%))、肺结核和艾滋病(22(18.2%))以及疟疾(12(9.92%)。药物计量学在非洲的发展势头日益强劲,自创立以来所取得的进展将大大提高用于治疗艾滋病、结核病和其他新病症的治疗药物的安全性和有效性。
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引用次数: 0
Highlighted Articles 重点文章
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-20 DOI: 10.1002/cpt.3376
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引用次数: 0
Getting the Dosage Right: A Vital Role for Clinical Pharmacology in the Era of Precision Medicine 正确掌握剂量:精准医学时代临床药理学的重要作用》。
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-20 DOI: 10.1002/cpt.3375
Iris K. Minichmayr, Mohamad Shebley, Piet H. van der Graaf, Karthik Venkatakrishnan

Right dosage—administering the right dose at the right time in the optimal dosing interval using the appropriate application route and administration method—is central to the role of clinical pharmacology throughout the development and clinical use of therapeutics. It is critically important in all therapeutic areas to maximize patient benefit and minimize undesirable adverse effects. Getting the dosage right extends beyond population-level dosing to meet a certain efficacy or toxicity threshold in a defined patient group or subgroup of interest, such as patients with a specific indication or certain degree of organ impairment. As the “one-size-fits-all” concept often fails to optimize the benefit–risk ratio for all patients in clinical practice, various precision dosing strategies, acknowledging between-patient variability in exposure and/or response, have been evolving to tailor dosage regimens and increase the chances of treatment success for individual patients. Just as a sculptor meticulously chisels away at a block of marble to reveal a masterpiece, dose finding in drug development and precision dosing involves carefully tailoring dosage regimens to the disease of concern and the unique characteristics of patients (Figure 1). This special-themed issue of Clinical Pharmacology & Therapeutics illuminates various aspects, advancements, and future perspectives in getting the dosage right in drug development, regulatory approval, and clinical practice.

Dose selection and optimization have been particularly prominent topics in oncology in recent years, not least since the launch of Project Optimus by the US Food and Drug Administration.1 This initiative aims to reform dose selection to maximize not only the efficacy of a drug, but also its safety and tolerability. In this issue, two papers provide comprehensive viewpoints on the topic of oncology dosage optimization from the regulatory and pharmaceutical industry sectors, respectively. In their State-of-the-Art review, Rahman et al. offer a regulatory perspective highlighting the foundational importance of timely dosage optimization and the consequences of not doing so.2 The authors discuss the topic in the context of the realities of rapid development programs, rare and pediatric cancers, and combination development, outlining the value of tools in translational and precision medicine, and model-informed drug development for achieving the desired objectives. A White Paper by the Oncology Dose Optimization Working Group, commissioned by the International Consortium for Innovation and Quality in Pharmaceutical Development, highlights the impact of Project Optimus on oncology dose optimization, together with common issues and potential solutions, post-marketing requirements and commitments, as well as insights from a survey on current industry practices for oncology dose selection.3 The

18 虽然该领域的进展为提高精准给药带来了希望,但要将其临床应用到医疗保健生态系统中,还需要在临床实践环境中推广此类研究,并推进相关的监管框架和政策制定,以弥合从实验室到床边的差距,充分实现这些创新的前景。虚拟双胞胎研究还揭示了与药物代谢和处置相关的 500 个酶和转运体靶点的 mRNA 表达,这只是挑战 "一刀切 "方法之外的 "一靶点万能 "理念的一个例子。19 用于剂量优化的临床定量药理学方法正以惊人的创新速度向前发展,生物学驱动的疾病模型的进步和数据科学的创新使系统医学框架得以注入。定量系统药理学(QSP)模型考虑了先天性免疫反应和适应性免疫反应等生物系统的详细组成部分,因此具有很高的机理可解释性。本期 CPT 内容包括通过预测对抗病毒疗法的反应来帮助在紧急健康危机期间进行有模型指导的决策的 QSP 框架20,以及一个案例研究,该案例研究说明了如何利用 QSP 模型进行有模型指导的精确用药21。机器学习方法也已进入用药研究领域,例如,在开发有模型指导的精确用药算法以支持更安全、更有效的处方22。23 剂量优化方面的创新对于在新适应症和患者群体监管审批的效益/风险评估背景下生成证据至关重要。Al-Khouja 等人在文章中从监管角度阐述了 FDA 批准霉酚酸酯(mycophenolate mofetil)用于预防小儿心脏或肝脏移植患者的器官排斥反应,他们概述了支持定义适当剂量范围的证据,这些证据利用了从成人环境中进行外推的原则,以及整合了特定适应症和人群中所有可用知识的证据整体方法。针对儿童群体的药物开发需要全面评估体型/体重和年龄对全身暴露的影响,以确定适当的剂量。25 一项回顾性数据库审查对当前的剂量策略,特别是体型对剂量结果的影响进行了描述,并与成人剂量策略进行了比较。药物研发成功并获得批准后,在临床实践中采用适当的给药剂量是关键,但也并非无足轻重,有报告指出真实世界临床结果的价值27 以及批准后在特定人群中持续优化剂量,即使是万古霉素和他莫昔芬等已在临床实践中使用数十年的老药也是如此28,29。然而,正如 Abdel-Rahman 等人和 Morales Junior 等人在他们的行动呼吁中所讨论的那样,TDM 在许多药物中的作用还存在争议,在医疗保健生态系统中将其转化为临床实践还有许多机会。例如,一个 CDS 应用程序有可能加强镰状细胞贫血患儿的羟基脲治疗,尤其是在没有临床药理学专业知识的地方34。现在有机会扩展此类应用程序,不仅纳入 PK 数据,还纳入相关的药效学/安全性生物标志物数据,并使用机理性联合群体 PK-PD 模型进行整合35。目前还在努力简化采样和居家 PK 测量,以便调整用药剂量,如另一项研究所示,该研究评估了以患者为中心的低容量毛细管液体和干血采样设备,适用于各种大分子和小分子药物。
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引用次数: 0
Model-Informed Approaches to Optimizing Therapeutics in the African Patient Populations. 在非洲患者群体中优化治疗方法的模型启发法。
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-20 DOI: 10.1002/cpt.3425
Mwila Mulubwa, Kelly Chibale
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引用次数: 0
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Clinical Pharmacology & Therapeutics
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