Li Jiayu, Hu Pei, Zhou Li, Nagahama Fumiko, Chen Rui
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Front Pharmacol. 2023 Jun 26;14:1154026. doi: 10.3389/fphar.2023.1154026. eCollection 2023.
Granisetron patches are a prolonged delivery transdermal system that is used to prevent Chemotherapy-induced nausea and vomiting (CINV). To date, no pharmacokinetics comparison between Chinese and Caucasian populations has been conducted for granisetron patches. This study focused on the ethnic differences in pharmacokinetics (PK) of granisetron transdermal delivery system (GTDS) between Chinese and Caucasians and the influence of demographic covariates on pharmacokinetics (age, weight, height, body mass index, sex). To achieve this, blood concentration data were collected from 112 Caucasian healthy subjects participating in four clinical trials and 24 Chinese healthy subjects from one clinical trial, after a single application of the granisetron transdermal delivery system. A nonlinear mixed-effects model method of Phoenix NLME software was used to establish a population pharmacokinetic (Pop PK) model for Caucasian subjects. Bootstrap and visual predictive check (VPC) were used to validate the model. Based on the analysis a one-compartment model with first-order absorption and a first-order elimination well described the PK characteristics of GTDS. The apparent systemic clearance was determined to be 31316.3 mL/h and the central compartment volume of distribution was 6299.03 L. None of the five covariates (age, weight, height, body mass index, and sex) included in the Pop PK were significant covariates affecting PK. The final Pop PK model was used to simulate the Caucasian blood concentration by applying the dosing regimen used for the Chinese population. Comparison of the simulated Caucasian PK data with observed clinical PK data from Chinese healthy subjects revealed no significant differences in the main parameters, AUC and C, between the two groups. These findings suggested that no dose adjustment was required when applied to the Chinese population. In conclusion, this Pop PK study comparing the transdermal patch in Chinese and Caucasian healthy subjects provided valuable insights for optimizing dosage across ethnicities.
格拉司琼贴片是一种长效透皮给药系统，用于预防化疗引起的恶心和呕吐（CINV）。迄今为止，尚未对中国人群和白种人群之间的格拉司琼贴片进行药代动力学比较。本研究聚焦于中国人群和白种人群之间格拉司琼透皮给药系统（GTDS）药代动力学（PK）的种族差异，以及人口统计学协变量（年龄、体重、身高、体重指数、性别）对药代动力学的影响。为此，在单次应用格拉司琼透皮给药系统后，收集了参与四项临床试验的112名白种健康受试者和一项临床试验的24名中国健康受试者的血药浓度数据。使用Phoenix NLME软件的非线性混合效应模型方法为白种受试者建立群体药代动力学（Pop PK）模型。采用自举法和可视化预测检查（VPC）对模型进行验证。基于分析，具有一级吸收和一级消除的单室模型很好地描述了GTDS的PK特征。表观全身清除率确定为31316.3 mL/h，中央室分布容积为6299.03 L。Pop PK中纳入的五个协变量（年龄、体重、身高、体重指数和性别）均不是影响PK的显著协变量。最终的Pop PK模型用于通过应用中国人群使用的给药方案模拟白种人的血药浓度。将模拟的白种人PK数据与中国健康受试者观察到的临床PK数据进行比较，发现两组之间主要参数AUC和C无显著差异。这些发现表明，应用于中国人群时无需调整剂量。总之，这项比较中国和白种健康受试者透皮贴片的Pop PK研究为跨种族优化剂量提供了有价值的见解。
