Pharmacokinetic-pharmacodynamic modeling and simulation:concepts and basic principles(1)

Abstract

Abstract: Modeling and simulation (M&S)is an important research field in pharmacokinetics and pharmacodynamics.M&S has evolved from a tool primarily applied to therapeutic drug monitoring to one that plays a significant role in drug development.Technological advances in various fields related to drug development call for more focus on ways to optimize current drug development practices.Recognition of the potential of M&S by regulatory agencies inevitably has a substantial impact on drug development.The objective of the current review is to present some of the basic concepts and principles of M&S.Case studies are presented to illustrate how M&S can facilitate knowledge management and decision making.In this article, introduction, definitions and background information of M&S are discussed.

Key words: pharmacokinetics, pharmacodynamics, mathematical model, modeling and simulation

CLC Number:

R911

HUANG Xiao-hui, SHI Jun, LI Jun, XIE Hai-tang, ZHENG Qing-shan, SUN Rui-yuan. Pharmacokinetic-pharmacodynamic modeling and simulation:concepts and basic principles(1)[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(1): 82-89.

References

[1] Bonate PL. Pharmacokinetic-pharmacodynamic modeling and simulation[M]. New York: Springer, 2005: 1-12.
[2] National Institutes of Health. Modeling in biomedical research: an assessment of current and potential approaches[M]. Maryland: 1989. http://dels.nas.edu/ilar_n/ilarjournal_32_2/32_2Modeling. shtml.
[3] Balant LP, Gex-Fabry M. Modeling during drug and development[J]. Eur J Pharm Sci, 2000;50: 13-26.
[4] Sheiner LB, Steimer JL. Pharmacokinetic Pharmacodynamic Modeling in drug development[J]. Annu Rev Pharmacol Toxicol, 2000;40: 67-95.
[5] 姜启源. 数学模型[M]. 第2 版. 北京: 高等教育出版社, 1993: 2-27.
[6] Zhang/LP, Vikram SS, Forgue T, et al. Model-based drug development: the road to quantitative pharmacology[J]. J Pharmacokinet Phar, 2006;33: 369-390.
[7] Gobburu JV, Marroum PJ. Utilisation of pharmacokinetic-pharmacodynamic modeling and simulation in regulatory decisionmaking[J]. Clin Pharmacokinet, 2001;40: 883-892.
[8] Rescigno A, Beck JS, ThakurAK. The use and abuse of models[J]. J Pharmacokinet Phar, 1987;15: 327-340.
[9] Thakur AK. Commentary on the article of A. Rescigno and J. S. Beck[J]. J Pharmacokinet Phar, 1987;15: 341-344.
[10] Wang QH. Estimation of partial linear error-in-variables model[J]. J Multivar Anal, 1999;69: 30-64.
[11] DiStefano JJ. The modeling methodology forum: an expanded department[J]. Am J Physiol Gastrointest Liver Physiol, 1985;248: 145-146.
[12] DiStefano JJ. A retrospective on the modeling methodology forum. The review process for modeling papers: a revisionist' s experiences and perspectives[J]. Am J Physiol, 1994;267: 485-488.
[13] Holford N, Sheiner L. Understanding the dose-effect relationship: clinical application of pharmacokinetic pharmacodynamics models[J]. Clin Pharmacokinet, 1981;6: 429-453.
[14] Holford N, Sheiner L. Pharmacokinetic and pharmacodynamics modeling in vivo[J]. CRC Crit Rev Bioeng, 1981;5: 273.
[15] Derendorf H, Meibohm B. Modeling of pharmacokinetic pharmacodynamics(PK PD) relationships: concepts and perspectives[J]. Pharm Res, 1999;16: 176-185.
[16] 黄晓晖, 裘福荣. 药动学药效学结合模型[A]. 见: 孙瑞元, 郑青山, 主编. 数学药理学新论[M]. 北京: 人民卫生出版社, 2004: 530-547