A Statistical Approach to the Pharmacokinetic Model

집단 약동학 모형에 대한 통계학적 고찰

Lee, Eun-Kyung

  • Received : 20100200
  • Accepted : 20100400
  • Published : 2010.06.30


The Pharmacokinetic model is a complex nonlinear model with pharmacokinetic parameters that is some-times represented by a complex form of differential equations. A population pharmacokinetic model adds individual variability using the random effects to the pharmacokinetic model. It amounts to the nonlinear mixed effect model. This paper, reviews the population pharmacokinetic model from a statistical viewpoint; in addition, a population pharmacokinetic model is also applied to the real clinical data along with a review of the statistical meaning of this model.


Population pharmacokinetics;mixed effect model;nonlinear function


  1. 강주섭, 강주희, 이민호 (2001). <임상약동학의 이해>, 도서출판 신일상사.
  2. 서울대학교 의과대학 (2006). <임상약리학>, 서울대학교 출판부.
  3. Atkinson, A. J., Abernethy, D. R., daniels, C. E., Dedrick, R. L. and Markey, S. P. (2007). Principles of Clinical Pharmacology, Elsevier, San Diego.
  4. Beal, S. B. and Sheiner, L. B. (1979). NONMEM User's Guide, Division of Clinical Pharmacology, University of California, San Francisco.
  5. Boeckmann, A. J., Sheiner, L. B. and Beal, S. L. (1994). NONMEM Users Guide: Part V, NONMEM Project Group, University of California, San Francisco.
  6. Davidian, M. and Giltinan, D. (1995). Nonlinear Models for Repeated Measurement Data, Chapman and Hall, London.
  7. DiPiro, J. T., Spruill, W. J., Wade, W. E., Blouin, R. A. and Pruemer, J. M. (2005). Concepts in Clinical Pharmacokinetics, American Society of Health-System Pharmacists.
  8. Gabrielsson, J. and Weiner, D. (2006). Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts and Applications, Apotekarsocieteten, Swedish Academy of Pharmaceutical Sciences.
  9. Gibaldi, M. and Levy, G. (1976). Pharmacokinetics in clinical practice, The Journal of the American Medical Association, 17, 1864-1867.
  10. Harville, D. (1977). Maximum likelihood approaches to variance component estimation and to related problems, Journal of the American Statistical Association, 72, 320-338.
  11. Jonsson, E. N. and Karlsson, M. O. (1999). Xpose-an S-PLUS based population pharmacokinetic/pharmacodynamic model building aid for NONMEM, Computer Methods and Programs in Biomedicine, 58, 51-64.
  12. Laird, N. M. and Ware, J. H. (1982). Random-effects models for longitudinal data, Biometrics, 38, 963-974.
  13. Lindstorm, M. J. and Bates, D. M. (1990). Nonlinear mixed effects models for repeated measures data, Biometrics, 46, 673-687.
  14. Racine-Poon, A. (1985). A Bayesian approach to nonlinear random effects models, Biometrics, 41, 1015-1023.
  15. Samson, A., Lavielle, M. and Mentre, F. (2007). The SAEM algorithm for group comparison tests in longitudinal data analysis based on non-linear mixed-effects model, Statistics in Medicine, 26, 4860-4975.
  16. Wagner, J. G. (1993). Pharmacokinetics for the Pharmaceutical Scientist, Technomic Publishing Co., Inc., Lancaster.
  17. Wakefiled, J. (1996). The Bayesian analysis of population pharmacokinetic models, Journal of the American Statistican Association, 91, 62-75.

Cited by

  1. Estimation Methods for Population Pharmacokinetic Models using Stochastic Sampling Approach vol.28, pp.2, 2015,


Supported by : 한국학술진흥재단