Mohammadi Jouabadi Soroush, Nekouei Shahraki Mitra, Peymani Payam, Stricker Bruno H, Ahmadizar Fariba
Department of Epidemiology, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, Netherlands.
Division of Pharmacology, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, Netherlands.
Front Pharmacol. 2022 Jun 20;13:908538. doi: 10.3389/fphar.2022.908538. eCollection 2022.
In human pharmacology, there are two important scientific branches: clinical pharmacology and pharmacoepidemiology. Pharmacokinetic/pharmacodynamic (PK/PD) modeling is important in preclinical studies and randomized control trials. However, it is rarely used in pharmacoepidemiological studies on the effectiveness and medication safety where the target population is heterogeneous and followed for longer periods. The objective of this literature review was to investigate how far PK/PD modeling is utilized in observational studies on glucose-lowering and antiarrhythmic drugs. A systematic literature search of MEDLINE, Embase, and Web of Science was conducted from January 2010 to 21 February 2020. To calculate the utilization of PK/PD modeling in observational studies, we followed two search strategies. In the first strategy, we screened a 1% random set from 95,672 studies on glucose-lowering and antiarrhythmic drugs on inclusion criteria. In the second strategy, we evaluated the percentage of studies in which PK/PD modeling techniques were utilized. Subsequently, we divided the total number of included studies in the second search strategy by the total number of eligible studies in the first search strategy. The comprehensive search of databases and the manual search of included references yielded a total of 29 studies included in the qualitative synthesis of our systematic review. Nearly all 29 studies had utilized a PK model, whereas only two studies developed a PD model to evaluate the effectiveness of medications. In total, 16 out of 29 studies (55.1%) used a PK/PD model in the observational setting to study effect modification. The utilization of PK/PD modeling in observational studies was calculated as 0.42%. PK/PD modeling techniques were substantially underutilized in observational studies of antiarrhythmic and glucose-lowering drugs during the past decade.
在人体药理学中，有两个重要的科学分支：临床药理学和药物流行病学。药代动力学/药效学（PK/PD）建模在临床前研究和随机对照试验中很重要。然而，在针对疗效和用药安全性的药物流行病学研究中，它很少被使用，因为这些研究的目标人群具有异质性且随访时间较长。这篇文献综述的目的是调查PK/PD建模在关于降糖药和抗心律失常药物的观察性研究中的应用程度。我们于2010年1月至2020年2月21日对MEDLINE、Embase和科学网进行了系统的文献检索。为了计算PK/PD建模在观察性研究中的应用情况，我们采用了两种检索策略。在第一种策略中，我们根据纳入标准从95672项关于降糖药和抗心律失常药物的研究中筛选出1%的随机样本。在第二种策略中，我们评估了使用PK/PD建模技术的研究的百分比。随后，我们将第二种检索策略中纳入研究的总数除以第一种检索策略中符合条件的研究的总数。对数据库的全面检索和对纳入参考文献的手动检索共产生了29项研究，纳入了我们系统评价的定性综合分析。几乎所有29项研究都使用了PK模型，而只有两项研究开发了PD模型来评估药物的有效性。在总共29项研究中，有16项（55.1%）在观察性研究中使用PK/PD模型来研究效应修正。PK/PD建模在观察性研究中的应用率计算为0.42%。在过去十年中，PK/PD建模技术在抗心律失常药物和降糖药物的观察性研究中未得到充分利用。
