Experimental design and efficient parameter estimation in population pharmacokinetics
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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.
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- Experimental design and efficient parameter estimation in population pharmacokinetics
Journal of Pharmacokinetics and Biopharmaceutics
Volume 18, Issue 4 , pp 347-360
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers-Plenum Publishers
- Additional Links
- computer simulation
- parameter estimation
- population pharmacokinetics
- experimental design
- Industry Sectors
- Author Affiliations
- 1. Department of Medicine and Therapeutics, University of Glasgow, Stobhiil General Hospital, G21 3UW, Glasgow, Scotland
- 3. Department of Clinical Physics & Bioengineering, West of Scotland Health Boards, 11 West Graham Street, G4 9LF, Glasgow, Scotland