Evaluation of methods for estimating population pharmacokinetic parameters. III. Monoexponential model: Routine clinical pharmacokinetic data
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Individual pharmacokinetic parameters quantify the pharmacokinetics of an individual, while population pharmacokinetic parameters quantify population mean kinetics, interindividual kinetic variability, and residual variability, including intraindividual variability and measurement error. Individual pharmacokinetics are estimated by fitting a pharmacokinetic model to individual data. Population pharmacokinetic parameters have traditionally been estimated by doing this separately for each individual, and then combining the individual parameter estimates, the Standard Two Stage (STS) approach. Another approach, NONMEM, appropriately pools data across individuals and is therefore less dependent on individual parameter estimates. This study provides further evidence of NONMEM's validity and usefulness by comparing both approaches on simulated routine-type pharmacokinetic data arising from a monoexponential model. The estimates of population parameters (notably those describing interindividual variability) provided by the STS method are poorer than those provided by NONMEM, especially when there is considerable residual error. Further, NONMEM's estimates of population parameters do not require that the data be restricted to special types of routine data such as those obtained only at steady state, or only at peak or trough, nor do the estimates improve with such data. NONMEM's estimates do improve, however, when a data set is enhanced by the addition of single-observation-per-individual type data. Thus, population parameters can be estimated efficiently from data that simulate real clinical pharmacokinetic conditions.
Key wordspharmacokinetic data analysis population pharmacokinetic parameters estimation statistics simulation
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- 3.S. L. Beal and L. B. Sheiner.NONMEM Users Guide, parts I & II. Technical Report, Division of Clinical Pharmacology, University of California, San Francisco (1980).Google Scholar
- 4.S. L. Beal. Asymptotic properties of optimization estimators for the independent not identically distributed case with application to extended least squares estimators. Technical Report, Division of Clinical Pharmacology, University of California, San Francisco (1982).Google Scholar
- 8.L. B. Sheiner and T. N. Tozer. Clinical Pharmacokinetics: the use of plasma concentrations of drugs. In K. L. Melmon and H. F. Morrelli (eds.),Clinical Pharmacology, 2nd ed. Macmillan, New York, 1978, pp. 71–109.Google Scholar