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PK/PD model

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Class of models in pharmacology

PK/PD modeling (pharmacokinetic/pharmacodynamic modeling) (alternatively abbreviated as PKPD or PK-PD modeling) is a technique that combines the two classical pharmacologic disciplines of pharmacokinetics and pharmacodynamics. 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.

Central to PK/PD models is the concentration-effect or exposure-response relationship. A variety of PK/PD modeling approaches exist to describe exposure-response relationships. PK/PD relationships can be described by simple equations such as linear model, Emax model or sigmoid Emax model. 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:

  • Direct vs Indirect link PK/PD models
  • Direct vs Indirect response PK/PD models
  • Time variant vs time invariant
  • Cell lifespan models
  • Complex response models

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

References

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  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): 633–48. doi:10.1111/j.1472-8206.2008.00633.x. PMID 19049668. S2CID 4979109.
  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. S2CID 23165736.
  4. Upton, Rn; Mould, Dr (2014). "Basic Concepts in Population Modeling, Simulation, and Model-Based Drug Development: Part 3-Introduction to Pharmacodynamic Modeling Methods". CPT: Pharmacometrics & Systems Pharmacology. 3 (1): 88. doi:10.1038/psp.2013.71. PMC 3917320. PMID 24384783.
  5. 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.
  6. Pharmaceutical Biotechnology: Fundamentals and Applications. Crommelin, Daan; Meibohm, Bernd; Sindelar, Robert. Third Edition. Informa Healthcare USA. 2008.
  7. 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.
  8. 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. doi:10.1007/BF01061691. ISSN 0090-466X. PMC 4207304. PMID 8133465.
  9. 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. ISSN 0928-0987. PMID 11297895.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  10. 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. PMID 18405847.
  11. 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. PMID 15733216.
  12. Food and Drug Administration (2018-08-24). "Exposure-Response Relationships — Study Design, Data Analysis, and Regulatory Applications". U.S. Food and Drug Administration. Retrieved 2022-05-09.


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