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Journal of Pharmacokinetics and Biopharmaceutics

, Volume 20, Issue 5, pp 529–556 | Cite as

Smooth nonparametric maximum likelihood estimation for population pharmacokinetics, with application to quinidine

  • Marie Davidian
  • A. Ronald Gallant
Pharmacometrics

Abstract

The seminonparametric (SNP) method, popular in the econometrics literature, is proposed for use in population pharmacokinetic analysis. For data that can be described by the nonlinear mixed effects model, the method produces smooth nonparametric estimates of the entire random effects density and simultaneous estimates of fixed effects by maximum likelihood. A graphical modelbuilding strategy based on the SNP method is described. The methods are illustrated by a population analysis of plasma levels in 136 patients undergoing oral quinidine therapy.

Key words

population pharmacokinetics nonlinear mixed effects models density estimation nonparametric estimation maximum likelihood quinidine 

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Copyright information

© Plenum Publishing Corporation 1992

Authors and Affiliations

  • Marie Davidian
    • 1
  • A. Ronald Gallant
    • 1
  1. 1.Department of StatisticsNorth Carolina State UniversityRaleigh

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