Estimation and inference in pharmacokinetic models: the effectiveness of model reformulation and resampling methods for functions of parameters.

Journal Article (Journal Article)

It is well known that high parameter estimate correlations and asymptotic variance estimates can cause estimation and inference problems in the analysis of pharmacokinetic models. In this paper we show that analysis of three important functions of pharmacokinetic parameters, the half-life, mean residence time, and the area under the curve, can sometimes be greatly improved by reformulating the model to address collinearity and by using the bootstrap to form confidence intervals. The resultant estimators can be more accurate than the original ones, and resultant confidence intervals can be narrower. Of the three measures, the half-life estimator is much better behaved than the estimators of mean residence time and area under the curve under collinearity, suggesting that it (or measures like it) should be used more often.

Full Text

Duke Authors

Cited Authors

  • Niedzwiecki, D; Simonoff, JS

Published Date

  • August 1990

Published In

Volume / Issue

  • 18 / 4

Start / End Page

  • 361 - 377

PubMed ID

  • 2231325

International Standard Serial Number (ISSN)

  • 0090-466X

Digital Object Identifier (DOI)

  • 10.1007/BF01062274


  • eng

Conference Location

  • United States