Non-linear mixed-effects pharmacokinetic/pharmacodynamic modelling in NLME using differential equations

Comput Methods Programs Biomed. 2004 Oct;76(1):31-40. doi: 10.1016/j.cmpb.2004.01.001.

Abstract

The standard software for non-linear mixed-effect analysis of pharmacokinetic/pharmacodynamic (PK/PD) data is NONMEM while the non-linear mixed-effects package NLME is an alternative as long as the models are fairly simple. We present the nlmeODE package which combines the ordinary differential equation (ODE) solver package odesolve and the non-linear mixed effects package NLME thereby enabling the analysis of complicated systems of ODEs by non-linear mixed-effects modelling. The pharmacokinetics of the anti-asthmatic drug theophylline is used to illustrate the applicability of the nlmeODE package for population PK/PD analysis using the available data analysis tools in R for model inspection and validation. The nlmeODE package is numerically stable and provides accurate parameter estimates which are consistent with NONMEM estimates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Bronchodilator Agents / pharmacokinetics
  • Bronchodilator Agents / pharmacology
  • Computer Simulation
  • Computers
  • Drug Design*
  • Drug Industry / methods*
  • Mathematical Computing
  • Models, Statistical
  • Models, Theoretical
  • Pharmacokinetics*
  • Software
  • Theophylline / pharmacokinetics*
  • Theophylline / pharmacology*

Substances

  • Bronchodilator Agents
  • Theophylline