Journal of Pharmacokinetics and Biopharmaceutics

, Volume 18, Issue 4, pp 347–360

Experimental design and efficient parameter estimation in population pharmacokinetics

  • Mahir K. Al-Banna
  • Andrew W. Kelman
  • Brian Whiting
Pharmacometrics

Abstract

A computer simulation technique used to evaluate the influence of several aspects of sampling designs on the efficiency of population pharmacokinetic parameter estimation is described. Although the simulations are restricted to the one-compartment one-exponential model, they provide the basis for a discussion of the structural aspects involved in designing a population study. These aspects include number of subjects required, number of samples per subject, and timing of these samples. Parameter estimates obtained from different sampling schedules based on two- and three-point designs are evaluated in terms of accuracy and precision. These simulated data sets include noise terms for both inter- and intraindividual variability. The results show that the population fixed-effect parameters (mean clearance and mean volume of distribution) for this simple pharmacokinetic model are efficiently estimated for most of the sampling schedules when two or three points are used, but the random-effect parameters (describing inter- and intraindividual variability) are inaccurate and imprecise for most of the sampling schedules when only two points are used. This drawback was remedied by increasing the number of data points per individual to three.

Key words

computer simulation parameter estimation population pharmacokinetics experimental design 

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Copyright information

© Plenum Publishing Corporation 1990

Authors and Affiliations

  • Mahir K. Al-Banna
    • 1
  • Andrew W. Kelman
    • 2
  • Brian Whiting
    • 1
  1. 1.Department of Medicine and TherapeuticsUniversity of Glasgow, Stobhiil General HospitalGlasgowScotland
  2. 2.Department of Clinical Physics & BioengineeringWest of Scotland Health BoardsGlasgowScotland
  3. 3.BIOSBagshotEngland

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