A two-step iterative algorithm for estimation in nonlinear mixed-effect models with an evaluation in population pharmacokinetics

J Biopharm Stat. 1995 Jul;5(2):141-58. doi: 10.1080/10543409508835104.

Abstract

This article proposes an EM-like algorithm for estimating, by maximum likelihood, the population parameters of a nonlinear mixed-effect model given sparse individual data. The first step involves Bayesian estimation of the individual parameters. During the second step, population parameters are estimated using a linearization about those Bayesian estimates. This algorithm (implemented in P-PHARM) is evaluated on simulated data, mimicking pharmacokinetic analyses and compared to the First-Order method and the First-Order Conditional Estimates method (both implemented in NONMEM). The accuracy of the results, within few iterations, shows the estimation capabilities of the proposed approach.

MeSH terms

  • Algorithms*
  • Humans
  • Models, Biological
  • Pharmaceutical Preparations / administration & dosage
  • Pharmacokinetics*
  • Population
  • Therapeutic Equivalency

Substances

  • Pharmaceutical Preparations