Chapter 1 Introduction

The aim of pharmacokinetics (PK) studies is to examine the kinetics of a drug with regard to absorption, distribution, metabolism and elimination in the body. PK data analysis consists of noncompartmental analysis (NCA) and nonlinear regression analysis. (Acharya et al. 2016; Gabrielsson 2016) NCA uses the trapezoidal rule for measurement of area under the concentration-time curve (AUC), and requires fewer assumptions than model-based analysis. (Gabrielsson 2016) NCA allows for estimation of various PK parameters such as AUC, peak observed drug concentration (C_max), time of peak concentration (T_max), and elimination half-life. Particularly, AUC and C_max are often accepted as the criteria for approval of bioequivalent drugs.

R, a widely-used computer language, is a suite of libraries of statistical and mathematical computations. (R Core Team 2018) Despite its relatively small base system compared with other commercial softwares for NCA such as WinNonlin®[4] and Kinetica,[5] R has robust functions for scientific computation and numerous add-in packages for use in various fields. (Kim, Yim, and Bae 2015) Therefore, many efforts are being made to replace commercial softwares with R packages.

In this article, we introduce two newly-developed R packages, NonCompart (Bae 2018 b) and ncar (Bae 2018 a), that are compatible with SDTM (Study Data Tabulation Model)-formatted dataset of CDISC (Clinical Data Interchange Standards Consortium), which is the standard of documentation submitted to regulatory authorities,[7] while providing a practical method for producing complete NCA reports. (Kim et al. 2018)

References

Acharya, Chayan, Andrew C Hooker, Gülbeyaz Yildiz Türkyilmaz, Siv Jönsson, and Mats O Karlsson. 2016. “A Diagnostic Tool for Population Models Using Non-Compartmental Analysis: The Ncappc Package for R.” Computer Methods and Programs in Biomedicine 127. Elsevier:83–93.

Gabrielsson, Johan. 2016. Pharmacokinetic and Pharmacodynamic Data Analysis : Concepts and Applications. Stockholm: Apotekarsocieteten.

R Core Team. 2018. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing. https://www.R-project.org/.

Kim, Min-Gul, Dong-Seok Yim, and Kyun-Seop Bae. 2015. “R-Based Reproduction of the Estimation Process Hidden Behind Nonmem Part 1: First-Order Approximation Method.” Translational and Clinical Pharmacology 23 (1):1–7.

Bae, Kyun-Seop. 2018b. NonCompart: Noncompartmental Analysis for Pharmacokinetic Data. https://CRAN.R-project.org/package=NonCompart.

Bae, Kyun-Seop. 2018a. Ncar: Noncompartmental Analysis for Pharmacokinetic Report. https://CRAN.R-project.org/package=ncar.

Kim, Hyungsub, Sungpil Han, Yong-Soon Cho, Seok-Kyu Yoon, and Kyun-Seop Bae. 2018. “Development of R Packages: ’NonCompart’ and Ncar for Noncompartmental Analysis (Nca).” Translational and Clinical Pharmacology 26 (1). Korean Society for Clinical Pharmacology; Therapeutics (KAMJE):10. https://doi.org/10.12793/tcp.2018.26.1.10.