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Drug-drug interactions between psychotropic medications and oral contraceptives. 精神药物和口服避孕药之间的药物相互作用。
IF 4.3 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-06-01 Epub Date: 2022-08-05 DOI: 10.1080/17425255.2022.2106214
Georgios Schoretsanitis, Kristina M Deligiannidis, Michael Paulzen, Edoardo Spina, Jose de Leon

Introduction: This is a comprehensive overview of pharmacokinetic drug-drug interactions (DDIs) involving oral contraceptives (OCs) and psychotropic medications.

Areas covered: Medline and Embase from inception to April 2021 were searched for DDIs between OCs and psychotropic medications. They included case reports/series and cross-sectional, cross-over, placebo-controlled studies of patient cohorts and healthy females. We classified DDIs as: combined hormonal contraceptives (CHCs) acting as victim drugs (i.e. affected by psychotropic co-medications), CHCs as perpetrators, (i.e. affecting the activity of psychotropic co-medications), progestin-derivatives as victim drugs and progestin-derivatives affecting psychotropic co-medications. Alteration ratios reflecting changes in pharmacokinetic parameters before and after the DDI were estimated to approximate the extent of the DDI.

Expert opinion: Women taking antiepileptic agents with strong to moderate enzyme-inducing properties (carbamazepine, phenobarbital, phenytoin) or those with moderate to mild enzyme-inducing properties (cenobamate, clobazam, eslicarbazepine, felbamate, oxcarbazepine, rufinamide, topiramate) should avoid OCs. Daily doses of cytochrome P450 1A2 substrates including clozapine may need to be reduced by 50% in women taking concomitant CHCs. Compared to CHCs, the propensity of progestin-only pills for DDIs has been investigated less. We provide a summary table for clinicians containing recommendations based on literature and package inserts; whenever evidence was available, we provided dose-correction factors.

简介:这是一个涉及口服避孕药(OCs)和精神药物的药代动力学药物相互作用(ddi)的全面概述。涵盖领域:Medline和Embase从成立到2021年4月检索OCs和精神药物之间的ddi。它们包括病例报告/系列和横断面、交叉、安慰剂对照的患者队列和健康女性研究。我们将ddi分类为:联合激素避孕药(CHCs)作为受害者药物(即受精神药物联合药物的影响),CHCs作为肇事者(即影响精神药物联合药物的活性),孕激素衍生物作为受害者药物和孕激素衍生物影响精神药物联合药物。估计DDI前后药代动力学参数变化的变化率,以近似DDI的程度。专家意见:服用具有强至中度酶诱导特性的抗癫痫药物(卡马西平、苯巴比妥、苯妥英)或具有中至轻度酶诱导特性的抗癫痫药物(辛奥巴酸、氯巴赞、埃斯卡巴西平、非胺酸、奥卡西平、鲁非胺、托吡酯)的妇女应避免服用OCs。合并CHCs的女性,包括氯氮平在内的细胞色素P450 1A2底物的日剂量可能需要减少50%。与CHCs相比,仅使用孕激素药物治疗ddi的倾向研究较少。我们为临床医生提供了一个总结表,其中包含基于文献和包装说明书的建议;只要有证据,我们就提供剂量校正因子。
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引用次数: 9
Review and evaluation of vancomycin dosing guidelines for obese individuals. 肥胖人群万古霉素给药指南的回顾与评价。
IF 4.3 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-05-01 Epub Date: 2022-07-17 DOI: 10.1080/17425255.2022.2098106
Sherilyn Wong, Stephanie E Reuter, Graham Rd Jones, Sophie L Stocker

Introduction: Vancomycin dosing decisions are informed by factors such as body weight and renal function. It is important to understand the impact of obesity on vancomycin pharmacokinetics and how this may influence dosing decisions. Vancomycin dosing guidelines use varied descriptors of body weight and renal function. There is uncertainty whether current dosing guidelines result in attainment of therapeutic targets in obese individuals.

Areas covered: Literature was explored using PubMed, Embase, and Google Scholar for articles from January 1980 to July 2021 regarding obesity-driven physiological changes, their influence on vancomycin pharmacokinetics and body size descriptors and renal function calculations in vancomycin dosing. Pharmacokinetic simulations reflective of international vancomycin dosing guidelines were conducted to evaluate the ability of using total, ideal, and adjusted body weight, as well as Cockcroft-Gault and CKD-EPI equations to attain an area-under-the-curve to minimum inhibitory concentration ratio (AUC24/MIC) target (400-650) in obese individuals.

Expert opinion: Vancomycin pharmacokinetics in obese individuals remains debated. Guidelines that determine loading doses using total body weight, and maintenance doses adjusted based on renal function and adjusted body weight, may be most appropriate for obese individuals. Use of ideal body weight leads to subtherapeutic vancomycin exposure and underestimation of renal function.

万古霉素的剂量决定是由体重和肾功能等因素决定的。了解肥胖对万古霉素药代动力学的影响以及这可能如何影响给药决定是很重要的。万古霉素剂量指南使用不同的体重和肾功能描述。目前的剂量指南是否能使肥胖患者达到治疗目标还不确定。涉及领域:利用PubMed、Embase和Google Scholar检索1980年1月至2021年7月期间有关肥胖驱动的生理变化、其对万古霉素药代动力学和体型描述符的影响以及万古霉素剂量下肾功能计算的文章。根据国际万古霉素给药指南进行了药代动力学模拟,以评估使用总体重、理想体重和调整体重以及Cockcroft-Gault和CKD-EPI方程在肥胖个体中获得曲线下面积与最小抑制浓度比(AUC24/MIC)目标(400-650)的能力。专家意见:万古霉素在肥胖个体中的药代动力学仍有争议。根据总体重确定负荷剂量,并根据肾功能和调整体重调整维持剂量的指南可能最适合肥胖个体。使用理想体重会导致治疗性万古霉素暴露和低估肾功能。
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引用次数: 1
Pharmacodynamics of Janus kinase inhibitors for the treatment of atopic dermatitis. Janus激酶抑制剂治疗特应性皮炎的药效学研究。
IF 4.3 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-05-01 Epub Date: 2022-07-12 DOI: 10.1080/17425255.2022.2099835
Laura Calabrese, Andrea Chiricozzi, Clara De Simone, Barbara Fossati, Alessandra D'Amore, Ketty Peris

Introduction: Atopic dermatitis (AD) is the most common inflammatory skin disorder. Despite the high disease burden, the therapeutic options are limited and their efficacy in controlling AD might be partially satisfactory.

Areas covered: Most of the key mediators in AD pathogenesis act through the JAK/STAT signaling pathway, which represents a valid therapeutic target. The first generation of JAK inhibitors, namely tofacitinib and ruxolitinib, inhibit multiple JAKs, whereas newer JAK inhibitors show more selective inhibitory effects for specific JAKs. The aim of this review was to discuss the role of the JAK/STAT pathway in AD and its inhibition, with a special focus on pharmacodynamic properties.

Expert opinion: JAK inhibitors have different selectivity for various JAK molecules, which influences their pharmacodynamics, efficacy, and safety profile. Since many key cytokines in AD signal through JAK1, the selective JAK1 inhibition may be effective, avoiding the concomitant inhibition of JAK2- and JAK3-dependent pathways could be associated with additional safety issues. Therefore, selective JAK1 inhibitors may represent promising therapeutic agents for AD, as they might prevent off-target effects of JAK inhibitors, especially related to the hematologic profile.

特应性皮炎(AD)是最常见的炎症性皮肤病。尽管疾病负担高,但治疗选择有限,其控制AD的效果可能部分令人满意。涉及领域:AD发病机制中的大多数关键介质通过JAK/STAT信号通路起作用,这是一个有效的治疗靶点。第一代JAK抑制剂,即tofacitinib和ruxolitinib,抑制多种JAK,而较新的JAK抑制剂对特定的JAK表现出更多的选择性抑制作用。本综述的目的是讨论JAK/STAT通路在AD及其抑制中的作用,并特别关注药效学特性。专家意见:JAK抑制剂对不同的JAK分子有不同的选择性,这影响了它们的药效学、疗效和安全性。由于AD中的许多关键细胞因子通过JAK1信号传导,选择性JAK1抑制可能是有效的,避免JAK2-和jak3依赖性途径的伴随抑制可能与额外的安全性问题相关。因此,选择性JAK1抑制剂可能是治疗AD的有希望的药物,因为它们可能阻止JAK抑制剂的脱靶效应,特别是与血液学特征相关的脱靶效应。
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引用次数: 4
Strategies for enhancing the oral bioavailability of cannabinoids. 提高大麻素口服生物利用度的策略。
IF 4.3 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-05-01 Epub Date: 2022-07-18 DOI: 10.1080/17425255.2022.2099837
Ayala Bar-Hai, Abraham J Domb, Amnon Hoffman

Introduction: Oral administration of cannabinoids is a convenient route of administration in many cases. To enhance the poor and variable bioavailability of cannabinoids, selected strategies utilizing proper delivery systems have been designed. Low solubility in the GI aqueous media is the first and most critical barrier. Thereafter, cannabinoids can reach the systemic blood circulation via the portal vein that is associated with significant hepatic first pass metabolism (FPM) or bypass it via lymphatic absorption.

Areas covered: The solubility obstacle of cannabinoids is mainly addressed with lipid-based formulations such as self-nanoemulsifying drug delivery systems (SNEDDS). Certain lipids are used to overcome the solubility issue. Surfactants and other additives in the formulation have additional impact on several barriers, including dictating the degree of lymphatic bioavailability and hepatic FPM. Gastro-retentive formulation is also plausible.

Expert opinion: Comparison of the role of the same SNEDDS formulation, cyclosporine vs. cannabinoids, when used to elevate the oral bioavailability of different compounds, is presented. It illustrates some similarities and major mechanistic differences obtained by the same SNEDDS. Thus, the different influence over the absorption pathway illuminates the importance of understanding the absorption mechanism and its barriers to properly select appropriate strategies to achieve enhanced oral bioavailability.

简介:在许多情况下,口服大麻素是一种方便的给药途径。为了提高大麻素的不良和可变的生物利用度,已经设计了利用适当的输送系统的选择策略。在GI水介质中的溶解度低是第一个也是最关键的障碍。此后,大麻素可以通过门静脉进入全身血液循环,这与显著的肝首过代谢(FPM)有关,或通过淋巴吸收绕过它。涉及领域:大麻素的溶解度障碍主要是通过脂基配方解决的,如自纳米乳化药物输送系统(SNEDDS)。某些脂质被用来克服溶解度问题。配方中的表面活性剂和其他添加剂对几个屏障有额外的影响,包括决定淋巴生物利用度和肝脏FPM的程度。胃保留配方也是合理的。专家意见:比较相同的SNEDDS制剂,环孢素和大麻素,当用于提高不同化合物的口服生物利用度时的作用,提出。它说明了相同的SNEDDS获得的一些相似之处和主要的机制差异。因此,对吸收途径的不同影响阐明了了解吸收机制及其障碍对于正确选择适当策略以提高口服生物利用度的重要性。
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引用次数: 5
An update on drug-drug interactions associated with proton pump inhibitors. 质子泵抑制剂与药物相互作用的最新进展。
IF 4.3 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-05-01 Epub Date: 2022-07-11 DOI: 10.1080/17425255.2022.2098107
Inès Ben Ghezala, Maxime Luu, Marc Bardou

Introduction: Proton pump inhibitors (PPIs) block the gastric H/K-ATPase, therefore inhibiting acid gastric secretion, leading to an increased pH (>4). They account for an extremely high number of prescriptions worldwide. Numerous drug-drug interactions have been described with PPIs, but all the described interactions do not have clinical significance.

Areas covered: This review will discuss the latest updates on drug-drug interactions with PPIs, focusing on the last 10-year publications in the following areas: anti-infective agents, anticancer drugs, antiplatelet agents and anticoagulants, and antidiabetics.

Expert opinion: Although pharmacokinetic interactions of PPIs have been described with many drugs, their clinical relevance remains controversial. However, given the extremely high number of people being treated with PPIs, clinicians should remain vigilant for interactions that may be clinically significant and require dose adjustment or therapeutic monitoring. Interestingly, not all PPIs have the same pharmacokinetic and pharmacodynamic profile, with some having a strong potential to inhibit CYP2C19, such as omeprazole, esomeprazole, and lansoprazole, while others, pantoprazole, rabeprazole, and dexlansoprazole, are weak CYP2C19 inhibitors. These may be preferred depending on co-prescribed treatments.In addition, new formulations have been developed to prevent some of the gastric pH-dependent drug interactions and should be evaluated in further large-scale prospective comparative studies.

质子泵抑制剂(PPIs)阻断胃H/ k - atp酶,从而抑制胃酸分泌,导致pH升高(>4)。它们在世界范围内的处方数量极高。许多药物-药物相互作用已被描述与PPIs,但所有描述的相互作用不具有临床意义。涵盖领域:本综述将讨论PPIs药物-药物相互作用的最新进展,重点关注过去10年在以下领域的出版物:抗感染药物、抗癌药物、抗血小板药物和抗凝血剂以及抗糖尿病药物。专家意见:尽管PPIs与许多药物的药代动力学相互作用已被描述,但其临床相关性仍存在争议。然而,鉴于接受质子泵抑制剂治疗的人数非常多,临床医生应该对可能具有临床意义的相互作用保持警惕,并需要调整剂量或进行治疗监测。有趣的是,并不是所有的PPIs都具有相同的药代动力学和药效学特征,一些PPIs具有很强的抑制CYP2C19的潜力,如奥美拉唑、埃索美拉唑和兰索拉唑,而其他PPIs,如泮托拉唑、雷贝拉唑和右兰索拉唑,是弱CYP2C19抑制剂。根据共同规定的治疗方法,这些可能是首选。此外,已经开发了新的配方来防止一些胃ph依赖性药物相互作用,应该在进一步的大规模前瞻性比较研究中进行评估。
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引用次数: 6
Current and future physiologically based pharmacokinetic (PBPK) modeling approaches to optimize pharmacotherapy in preterm neonates. 当前和未来基于生理的药代动力学(PBPK)建模方法优化早产儿药物治疗。
IF 4.3 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-05-01 Epub Date: 2022-07-15 DOI: 10.1080/17425255.2022.2099836
Karel Allegaert, Mohammad Yaseen Abbasi, Pieter Annaert, Olusola Olafuyi

Introduction: There is a need for structured approaches to inform on pharmacotherapy in preterm neonates. With their proven track record up to regulatory acceptance, physiologically based pharmacokinetic (PBPK) modeling and simulation provide a structured approach, and hold the promise to support drug development in preterm neonates.

Areas covered: Compared to general and pediatric use of PBPK modeling, its use to inform pharmacotherapy in preterms is limited. Using a systematic search (PBPK + preterm), we retained 25 records (20 research papers, 2 letters, 3 abstracts). We subsequently collated the published information on PBPK software packages (PK-Sim®, Simcyp®), and their applications and optimization efforts in preterm neonates. It is encouraging that applications cover a broad range of scenarios (pharmacokinetic-dynamic analyses, drug-drug interactions, developmental pharmacogenetics, lactation related exposure) and compounds (small molecules, proteins). Furthermore, specific compartments (cerebrospinal fluid, tissue) or (patho)physiologic processes (cardiac output, biliary excretion, first pass metabolism) are considered.

Expert opinion: Knowledge gaps exist, giving rise to various levels of uncertainty in PBPK applications in preterm neonates. To improve this, we need cross talk between clinicians and modelers to generate and integrate knowledge (PK datasets, system knowledge, maturational physiology and pathophysiology) to further refine PBPK models.

导言:需要结构化的方法来告知早产新生儿的药物治疗。基于生理的药代动力学(PBPK)建模和模拟提供了一种结构化的方法,并有望支持早产儿的药物开发。涉及领域:与PBPK模型的一般和儿科应用相比,其在早产儿药物治疗中的应用是有限的。通过系统检索(PBPK + preterm),我们保留了25条记录(20篇研究论文,2封信函,3篇摘要)。随后,我们整理了PBPK软件包(PK-Sim®,Simcyp®)及其在早产儿中的应用和优化工作的公开信息。令人鼓舞的是,应用涵盖了广泛的场景(药代动力学分析,药物-药物相互作用,发育药物遗传学,哺乳相关暴露)和化合物(小分子,蛋白质)。此外,还考虑了特定的腔室(脑脊液、组织)或(病理)生理过程(心输出量、胆排泄、第一次代谢)。专家意见:知识差距的存在,导致PBPK在早产儿中的应用存在不同程度的不确定性。为了改善这一点,我们需要临床医生和建模者之间的交流,以生成和整合知识(PK数据集、系统知识、成熟生理学和病理生理学),以进一步完善PBPK模型。
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引用次数: 3
CYP2D6 phenotypes and opioid metabolism: the path to personalized analgesia CYP2D6表型与阿片代谢:个体化镇痛的途径
IF 4.3 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-04-03 DOI: 10.1080/17425255.2022.2085552
P. Ballester, Javier Muriel, A. Peiró
ABSTRACT Introduction Opioids play a fundamental role in chronic pain, especially considering when 1 of 5 Europeans adults, even more in older females, suffer from it. However, half of them do not reach an adequate pain relief. Could pharmacogenomics help to choose the most appropriate analgesic drug? Areas covered The objective of the present narrative review was to assess the influence of cytochrome P450 2D6 (CYP2D6) phenotypes on pain relief, analgesic tolerability, and potential opioid misuse. Until December 2021, a literature search was conducted through the MEDLINE, PubMed database, including papers from the last 10 years. CYP2D6 plays a major role in metabolism that directly impacts on opioid (tramadol, codeine, or oxycodone) concentration with differences between sexes, with a female trend toward poorer pain control. In fact, CYP2D6 gene variants are the most actionable to be translated into clinical practice according to regulatory drug agencies and international guidelines. Expert Opinion CYP2D6 genotype can influence opioids’ pharmacokinetics, effectiveness, side effects, and average opioid dose. This knowledge needs to be incorporated in pain management. Environmental factors, psychological together with genetic factors, under a sex perspective, must be considered when you are selecting the most personalized pain therapy for your patients.
阿片类药物在慢性疼痛中起着重要作用,特别是考虑到五分之一的欧洲成年人(甚至更多的老年女性)患有慢性疼痛。然而,其中一半没有达到足够的疼痛缓解。药物基因组学能帮助选择最合适的镇痛药物吗?本综述的目的是评估细胞色素P450 2D6 (CYP2D6)表型对疼痛缓解、镇痛耐受性和潜在阿片类药物滥用的影响。直到2021年12月,通过MEDLINE, PubMed数据库进行文献检索,包括近10年的论文。CYP2D6在代谢中起主要作用,直接影响阿片类药物(曲马多、可待因或羟考酮)的浓度,性别差异明显,女性疼痛控制能力较差。事实上,根据监管药物机构和国际指南,CYP2D6基因变异是最有可能转化为临床实践的。专家意见CYP2D6基因型可影响阿片类药物的药代动力学、有效性、副作用和平均阿片类药物剂量。这些知识需要纳入疼痛管理。当你为你的病人选择最个性化的疼痛治疗时,必须从性别角度考虑环境因素、心理因素和遗传因素。
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引用次数: 3
Ceftazidime dosing in obese patients: is it time for more? 肥胖患者服用头孢他啶:是时候增加剂量了吗?
IF 4.3 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-04-03 DOI: 10.1080/17425255.2022.2080052
Cornélie Fanton D'Andon, Patricia Correia, J. Rigaill, B. Kably, Sophie Périnel-Ragey, M. Launay
ABSTRACT Introduction Ceftazidime is used for the treatment of many bacterial infections, including severe P. aeruginosa infections. Like other beta-lactams, inter-individual variability in ceftazidime pharmacokinetics has been described. Due to its related pathophysiological modifications, obesity might influence ceftazidime pharmacokinetics. Areas covered The objective of this review is to assess the current state of knowledge about the impact of obesity on ceftazidime treatment. A literature search was conducted on PubMed-MEDLINE (2016–2021) to retrieve pharmacokinetic studies published in English, matching the terms ‘ceftazidime’ AND ‘pharmacokinetics.’ Expert opinion The impact of obesity on pharmacokinetics is generally poorly known, mainly because obese patients are often excluded from clinical studies. However, the published literature clearly shows that obese patients have significantly lower ceftazidime concentrations. This could be explained by increased volume of distribution and clearance. This low exposure represents a major factor of therapeutic failure, potentially fatal for critically ill patients. While further studies would be useful to better assess the magnitude and understanding of this variability, the use of higher doses of ceftazidime is needed in obese patients. Moreover, therapeutic drug monitoring for dose adaptation is of major interest for these patients, as the efficacy of ceftazidime seems to be directly related to its plasma concentration.
头孢他啶用于治疗多种细菌感染,包括严重的铜绿假单胞菌感染。像其他β -内酰胺类药物一样,头孢他啶药代动力学的个体差异性已经被描述。由于其相关的病理生理改变,肥胖可能影响头孢他啶的药代动力学。本综述的目的是评估目前关于肥胖对头孢他啶治疗影响的知识状况。在PubMed-MEDLINE(2016-2021)上进行文献检索,检索已发表的英文药代动力学研究,匹配术语“头孢他啶”和“药代动力学”。专家意见肥胖对药代动力学的影响通常知之甚少,主要是因为肥胖患者经常被排除在临床研究之外。然而,已发表的文献清楚地表明,肥胖患者的头孢他啶浓度明显较低。这可能是由于分销和清仓量的增加。这种低暴露是治疗失败的一个主要因素,对危重病人来说可能是致命的。虽然进一步的研究将有助于更好地评估这种变异性的程度和理解,但肥胖患者需要使用更高剂量的头孢他啶。此外,治疗药物监测剂量适应是这些患者的主要兴趣,因为头孢他啶的疗效似乎与其血浆浓度直接相关。
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引用次数: 1
Drug–drug interactions involving antipsychotics and antihypertensives 包括抗精神病药物和抗高血压药物的药物相互作用
IF 4.3 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-04-03 DOI: 10.1080/17425255.2022.2086121
C. A. Buzea, L. Dima, C. Correll, P. Manu
ABSTRACT Introduction Antipsychotics represent the mainstay in the treatment of patients diagnosed with major psychiatric disorders. Hypertension, among other components of metabolic syndrome, is a common finding in these patients. For their psychiatric and physical morbidity, many patients receive polypharmacy, exposing them to the risk of clinically relevant drug–drug interactions. Areas covered This review summarizes the knowledge regarding the known or potential drug–drug interactions between antipsychotics and the main drug classes used in the treatment of hypertension. We aimed to provide the clinician an insight into the pharmacokinetic and pharmacodynamic interactions between these drugs for a better choice of combinations of drugs to treat both the mental illness and cardiovascular risk factors. For this, we performed a literature search in PubMed and Scopus databases, up to 31 July 2021. Expert opinion The main pharmacokinetic interactions between antipsychotics and antihypertensive drugs involve mainly the cytochrome P450 system. The pharmacodynamic interactions are produced by multiple mechanisms, leading to concurrent binding to the same receptors. The data available regarding drug–drug interactions is mostly based on case reports and small studies and therefore should be interpreted with caution. The current knowledge is sufficiently strong to guide clinicians in selecting safer drug combinations as summarized here.
摘要引言抗精神病药物是治疗被诊断为主要精神障碍患者的主要药物。在代谢综合征的其他组成部分中,高血压是这些患者的常见症状。由于他们的精神和身体发病率,许多患者接受多种药物治疗,使他们面临临床相关药物相互作用的风险。涵盖的领域本综述总结了抗精神病药物和用于治疗高血压的主要药物类别之间已知或潜在的药物-药物相互作用的知识。我们的目的是让临床医生深入了解这些药物之间的药代动力学和药效学相互作用,以便更好地选择药物组合来治疗精神疾病和心血管风险因素。为此,我们在PubMed和Scopus数据库中进行了文献检索,截至2021年7月31日。专家意见抗精神病药物和抗高血压药物之间的主要药代动力学相互作用主要涉及细胞色素P450系统。药效相互作用是由多种机制产生的,导致同时与同一受体结合。关于药物相互作用的现有数据主要基于病例报告和小型研究,因此应谨慎解读。目前的知识足够强大,可以指导临床医生选择更安全的药物组合,如下所述。
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引用次数: 3
Pharmacokinetic evaluation of cefiderocol for the treatment of multidrug resistant Gram-negative infections. 头孢地罗治疗多重耐药革兰氏阴性感染的药代动力学评价
IF 4.3 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-04-01 Epub Date: 2022-06-08 DOI: 10.1080/17425255.2022.2081148
Emily N Drwiega, Nicole C Griffith, Larry H Danziger

Introduction: Cefiderocol is a siderophore cephalosporin antibiotic and first of its kind approved by the Food and Drug Administration for the treatment of complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) in patients 18 years or older caused by susceptible organisms. Cefiderocol's unique mechanism of iron chelation improves Gram-negative membrane penetration as the bacteria's iron uptake mechanism recognizes the chelated iron antibiotic and iron for entry. This also allows for the evasion of cefiderocol from cell entry-related resistance mechanisms.

Areas covered: This review covers the mechanism of action, resistance mechanisms, pharmacokinetics in various patient populations, and pharmacodynamics. Relevant literature evaluating efficacy and safety are discussed.

Expert opinion: Limited treatment options are available for the treatment of carbapenem-resistantorganisms. Clinical trials have demonstrated that cefiderocol is no worse than alternative treatment options for cUTIs and HABP/VABP, but more data are currently available to support the use of beta-lactam beta-lactamase inhibitor agents, where susceptible. Mortality differences demonstrated in patients with pneumonia and bloodstream infections must further be explored and logistical and practical considerations regarding susceptibility testing and use as monotherapy vs. combination therapy must be considered prior to confidently recommending cefiderocol for regular use in systemic infections.

摘要简介头孢iderocol是一种铁载体头孢菌素类抗生素,首次被美国食品药品监督管理局批准用于治疗18岁及以上易感生物引起的复杂尿路感染(cUTI)、医院获得性和呼吸机相关细菌性肺炎(HABP/VABP)。Ceferderocol独特的铁螯合机制提高了革兰氏阴性菌膜的渗透性,因为细菌的铁吸收机制识别螯合的铁抗生素和铁进入。这也允许头孢iderocol逃避细胞进入相关的耐药性机制。涵盖的领域本综述涵盖了作用机制、耐药性机制、不同患者群体的药代动力学和药效学。对评价疗效和安全性的相关文献进行了讨论。专家意见可用于治疗碳青霉烯类耐药性有机物的治疗方案有限。临床试验表明,对于cUTI和HABP/VABP,头孢地罗醇并不比替代治疗方案差,但目前有更多数据支持在易感的情况下使用β-内酰胺酶抑制剂。必须进一步探讨肺炎和血液感染患者的死亡率差异,在自信地推荐头孢iderocol定期用于全身感染之前,必须考虑易感性测试和单药治疗与联合治疗的后勤和实际考虑。
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引用次数: 0
期刊
Expert Opinion on Drug Metabolism & Toxicology
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