PKPD modeling (pharmacokinetic pharmacodynamic modeling) (alternatively abbreviated as PK/PD[1] or PK-PD[2] modeling) is a technique that combines the two classical pharmacologic disciplines of pharmacokinetics and pharmacodynamics.[3] It integrates a pharmacokinetic and a pharmacodynamic model component into one set of mathematical expressions that allows the description of the time course of effect intensity in response to administration of a drug dose. PKPD modeling is related to the field of pharmacometrics.
Central to PKPD models is the concentration-effect or exposure-response relationship.[4] A variety of PKPD modeling approaches exist to describe exposure-response relationships. PKPD relationships can be described by simple equations such as linear model, Emax model or sigmoid Emax model.[5] However, if a delay is observed between the drug administration and the drug effect, a temporal dissociation needs to be taken into account and more complex models exist:[6][7]
PKPD modeling has its importance at each step of the drug development[9][10] and it has shown its usefulness in many diseases.[11] The Food and Drug Administration also provides guidances for Industry to recommend how exposure-response studies should be performed.[12]
References
^Hahn, J. O.; Khosravi, S.; Dumont, G. A.; Ansermino, J. M. (2011). "Two-stage vs mixed-effect approach to pharmacodynamic modeling of propofol in children using state entropy". Pediatric Anesthesia. 21 (6): 691–698. doi:10.1111/j.1460-9592.2011.03584.x. PMID21518104. S2CID23414752.
^Goutelle, S.; Maurin, M.; Rougier, F.; Barbaut, X.; Bourguignon, L.; Ducher, M.; Maire, P. (2008). "The Hill equation: A review of its capabilities in pharmacological modelling". Fundamental & Clinical Pharmacology. 22 (6): 633–48. doi:10.1111/j.1472-8206.2008.00633.x. PMID19049668. S2CID4979109.
^Derendorf, H.; Meibohm, B. (1999). "Modeling of pharmacokinetic/pharmacodynamic (PK/PD) relationships: Concepts and perspectives". Pharmaceutical Research. 16 (2): 176–185. doi:10.1023/A:1011907920641. PMID10100300. S2CID23165736.
^Meibohm, B.; Derendorf, H. (October 1997). "Basic concepts of pharmacokinetic/pharmacodynamic (PK/PD) modelling". International Journal of Clinical Pharmacology and Therapeutics. 35 (10): 401–413. ISSN0946-1965. PMID9352388.
^Pharmaceutical Biotechnology: Fundamentals and Applications. Crommelin, Daan; Meibohm, Bernd; Sindelar, Robert. Third Edition. Informa Healthcare USA. 2008.
^Mager, Donald E.; Wyska, Elzbieta; Jusko, William J. (2003-05-01). "Diversity of Mechanism-Based Pharmacodynamic Models". Drug Metabolism and Disposition. 31 (5): 510–518. doi:10.1124/dmd.31.5.510. ISSN0090-9556. PMID12695336.
^Aarons, L.; Karlsson, M. O.; Mentré, F.; Rombout, F.; Steimer, J. L.; van Peer, A.; COST B15 Experts (May 2001). "Role of modelling and simulation in Phase I drug development". European Journal of Pharmaceutical Sciences. 13 (2): 115–122. doi:10.1016/S0928-0987(01)00096-3. ISSN0928-0987. PMID11297895.{{cite journal}}: CS1 maint: numeric names: authors list (link)
^Rajman, Iris (2008-04-01). "PK/PD modelling and simulations: utility in drug development". Drug Discovery Today. 13 (7): 341–346. doi:10.1016/j.drudis.2008.01.003. PMID18405847.
