PK/PD models

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PK/PD modeling (pharmacokinetic/pharmacodynamic modeling) (alternatively abbreviated as PKPD[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. PK/PD modeling is related to the field of pharmacometrics.

There are a variety of PK/PD modeling approaches to describe exposure-response relationships. PK/PD relationships can be described by simple equations such as linear model, Emax model or sigmoid Emax model.[4] 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:[5][6]

  • Indirect link PK/PD models
  • Indirect response PK/PD models[7]
  • Cell Lifespan models
  • Complex response models

PK/PD modeling has its importance at each step of the drug development[8][9] and it has shown its usefulness in many diseases.[10] The Food and Drug Administration also provides guidances for Industry to recommend how exposure-response studies should be performed [1].

References[edit]

  1. ^ 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. PMID 21518104. 
  2. ^ 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. doi:10.1111/j.1472-8206.2008.00633.x. 
  3. ^ 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. PMID 10100300. 
  4. ^ 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. ISSN 0946-1965. PMID 9352388. 
  5. ^ Pharmaceutical Biotechnology: Fundamentals and Applications. Crommelin, Daan; Meibohm, Bernd; Sindelar, Robert. Third Edition. Informa Healthcare USA. 2008.
  6. ^ 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. ISSN 0090-9556. PMID 12695336. 
  7. ^ Dayneka, Natalie L.; Garg, Varun; Jusko, William J. (August 1993). "Comparison of Four Basic Models of Indirect Pharmacodynamic Responses". Journal of pharmacokinetics and biopharmaceutics. 21 (4): 457–478. ISSN 0090-466X. PMC 4207304Freely accessible. PMID 8133465. 
  8. ^ 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. ISSN 0928-0987. PMID 11297895. 
  9. ^ 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. 
  10. ^ Karlsson, Mats O.; Anehall, Therese; Friberg, Lena E.; Henningsson, Anja; Kloft, Charlotte; Sandström, Marie; Xie, Rujia (2005-03-01). "Pharmacokinetic/Pharmacodynamic Modelling in Oncological Drug Development". Basic & Clinical Pharmacology & Toxicology. 96 (3): 206–211. doi:10.1111/j.1742-7843.2005.pto960310.x. ISSN 1742-7843.