Nonparametric Methods in Population Pharmacokinetics.

Abstract

Population pharmacokinetic (PK) modeling is a widely used approach to analyze PK data obtained from groups of individuals, in both industry and academic research. The approach can also be used to analyze pharmacodynamic (PD) data and pooled PK/PD data. There are 2 main families of population PK methods: parametric and nonparametric. The objectives of this article are to present an overview of nonparametric methods used in population pharmacokinetic modeling and to explain their specific characteristics to inform scientists and clinicians about their potential value for data analysis, simulation, dosage design, and therapeutic drug monitoring (TDM). Nonparametric methods have several interesting characteristics for population PK analysis, including computation of exact likelihoods, the ability to accommodate parameter probability distributions of any shape (eg, non-Gaussian), and to detect subpopulations and outliers. Nonparametric population methods are also highly relevant for model-based TDM and design of individualized drug dosage regimens. Several algorithms have been developed to estimate model parameter values within an individual and compute that individual's dosage to achieve target drug exposure with maximum precision and accuracy. Nonparametric modeling methods for both population and individual PK analysis are available under user-friendly packages.