Jijie Li1, Kewei Yan2, Lisha Hou1, Xudong Du1, Ping Zhu1, Li Zheng3, Cairong Zhu4. 1. Department of Epidemiology and Biostatistics, West China School of Public Health, Sichuan University, China, No. 17 Section 3, Renmin South Road, Chengdu, 610041, Sichuan, China. 2. College of Mathematics, Sichuan University, China, No. 24 South Section 1, Yihuan Road, Chengdu, 610065, Sichuan, China. 3. GCP Center/Institute of Clinical Pharmacology, West China Hospital of Sichuan University, China, Guoxuexiang 37#, Chengdu, 610041, Sichuan, China. lzheng2005618@163.com. 4. Department of Epidemiology and Biostatistics, West China School of Public Health, Sichuan University, China, No. 17 Section 3, Renmin South Road, Chengdu, 610041, Sichuan, China. cairong.zhu@hotmail.com.
Abstract
BACKGROUND AND OBJECTIVES: Pharmacokinetic/pharmacodynamic link models are widely used in dose-finding studies. By applying such models, the results of initial pharmacokinetic/pharmacodynamic studies can be used to predict the potential therapeutic dose range. This knowledge can improve the design of later comparative large-scale clinical trials by reducing the number of participants and saving time and resources. However, the modeling process can be challenging, time consuming, and costly, even when using cutting-edge, powerful pharmacological software. Here, we provide a freely available R program for expediently analyzing pharmacokinetic/pharmacodynamic data, including data importation, parameter estimation, simulation, and model diagnostics. METHODS: First, we explain the theory related to the establishment of the pharmacokinetic/pharmacodynamic link model. Subsequently, we present the algorithms used for parameter estimation and potential therapeutic dose computation. The implementation of the R program is illustrated by a clinical example. The software package is then validated by comparing the model parameters and the goodness-of-fit statistics generated by our R package with those generated by the widely used pharmacological software WinNonlin. RESULTS: The pharmacokinetic and pharmacodynamic parameters as well as the potential recommended therapeutic dose can be acquired with the R package. The validation process shows that the parameters estimated using our package are satisfactory. CONCLUSIONS: The R program developed and presented here provides pharmacokinetic researchers with a simple and easy-to-access tool for pharmacokinetic/pharmacodynamic analysis on personal computers.
BACKGROUND AND OBJECTIVES: Pharmacokinetic/pharmacodynamic link models are widely used in dose-finding studies. By applying such models, the results of initial pharmacokinetic/pharmacodynamic studies can be used to predict the potential therapeutic dose range. This knowledge can improve the design of later comparative large-scale clinical trials by reducing the number of participants and saving time and resources. However, the modeling process can be challenging, time consuming, and costly, even when using cutting-edge, powerful pharmacological software. Here, we provide a freely available R program for expediently analyzing pharmacokinetic/pharmacodynamic data, including data importation, parameter estimation, simulation, and model diagnostics. METHODS: First, we explain the theory related to the establishment of the pharmacokinetic/pharmacodynamic link model. Subsequently, we present the algorithms used for parameter estimation and potential therapeutic dose computation. The implementation of the R program is illustrated by a clinical example. The software package is then validated by comparing the model parameters and the goodness-of-fit statistics generated by our R package with those generated by the widely used pharmacological software WinNonlin. RESULTS: The pharmacokinetic and pharmacodynamic parameters as well as the potential recommended therapeutic dose can be acquired with the R package. The validation process shows that the parameters estimated using our package are satisfactory. CONCLUSIONS: The R program developed and presented here provides pharmacokinetic researchers with a simple and easy-to-access tool for pharmacokinetic/pharmacodynamic analysis on personal computers.
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