PKPD model

PKPD modeling (pharmacokinetic pharmacodynamic modeling) (alternatively abbreviated as PK/PD{{Cite journal | last1 = Hahn | first1 = J. O. | last2 = Khosravi | first2 = S. | last3 = Dumont | first3 = G. A. | last4 = Ansermino | first4 = J. M. | title = Two-stage vs mixed-effect approach to pharmacodynamic modeling of propofol in children using state entropy | doi = 10.1111/j.1460-9592.2011.03584.x | journal = Pediatric Anesthesia | volume = 21 | issue = 6 | pages = 691–698 | year = 2011 | pmid = 21518104| s2cid = 23414752 }} or PK-PD{{Cite journal | last1 = Goutelle | first1 = S. | last2 = Maurin | first2 = M. | last3 = Rougier | first3 = F. | last4 = Barbaut | first4 = X. | last5 = Bourguignon | first5 = L. | last6 = Ducher | first6 = M. | last7 = Maire | first7 = P. | doi = 10.1111/j.1472-8206.2008.00633.x | title = The Hill equation: A review of its capabilities in pharmacological modelling | journal = Fundamental & Clinical Pharmacology | volume = 22 | issue = 6 | pages = 633–48 | year = 2008 | pmid = 19049668| s2cid = 4979109 }} modeling) is a technique that combines the two classical pharmacologic disciplines of pharmacokinetics and pharmacodynamics.{{Cite journal | last1 = Derendorf | first1 = H. | last2 = Meibohm | first2 = B. | title = Modeling of pharmacokinetic/pharmacodynamic (PK/PD) relationships: Concepts and perspectives | journal = Pharmaceutical Research | volume = 16 | issue = 2 | pages = 176–185 | doi = 10.1023/A:1011907920641 | year = 1999 | pmid = 10100300| s2cid = 23165736 }} 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.{{Cite journal |last1=Upton |first1=Rn |last2=Mould |first2=Dr |date=2014 |title=Basic Concepts in Population Modeling, Simulation, and Model-Based Drug Development: Part 3-Introduction to Pharmacodynamic Modeling Methods |journal=CPT: Pharmacometrics & Systems Pharmacology |language=en |volume=3 |issue=1 |pages=88 |doi=10.1038/psp.2013.71 |pmc=3917320 |pmid=24384783}} 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.{{Cite journal|last1=Meibohm|first1=B.|last2=Derendorf|first2=H.|date=October 1997|title=Basic concepts of pharmacokinetic/pharmacodynamic (PK/PD) modelling|journal=International Journal of Clinical Pharmacology and Therapeutics|volume=35|issue=10|pages=401–413|issn=0946-1965|pmid=9352388}} 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:Pharmaceutical Biotechnology: Fundamentals and Applications. Crommelin, Daan; Meibohm, Bernd; Sindelar, Robert. Third Edition. Informa Healthcare USA. 2008.{{Cite journal|last1=Mager|first1=Donald E.|last2=Wyska|first2=Elzbieta|last3=Jusko|first3=William J.|date=2003-05-01|title=Diversity of Mechanism-Based Pharmacodynamic Models|journal=Drug Metabolism and Disposition|language=en|volume=31|issue=5|pages=510–518|doi=10.1124/dmd.31.5.510|issn=0090-9556|pmid=12695336}}

Direct vs Indirect link PKPD models
Direct vs Indirect response PKPD models{{Cite journal|last1=Dayneka|first1=Natalie L.|last2=Garg|first2=Varun|last3=Jusko|first3=William J.|date=August 1993|title=Comparison of Four Basic Models of Indirect Pharmacodynamic Responses|journal=Journal of Pharmacokinetics and Biopharmaceutics|volume=21|issue=4|pages=457–478|issn=0090-466X|pmc=4207304|pmid=8133465|doi=10.1007/BF01061691}}
Time variant vs time invariant
Cell lifespan models
Complex response models

PKPD modeling has its importance at each step of the drug development{{Cite journal|last1=Aarons|first1=L.|last2=Karlsson|first2=M. O.|last3=Mentré|first3=F.|last4=Rombout|first4=F.|last5=Steimer|first5=J. L.|last6=van Peer|first6=A.|last7=COST B15 Experts|date=May 2001|title=Role of modelling and simulation in Phase I drug development|journal=European Journal of Pharmaceutical Sciences|volume=13|issue=2|pages=115–122|issn=0928-0987|pmid=11297895|doi=10.1016/S0928-0987(01)00096-3}}{{Cite journal|last=Rajman|first=Iris|date=2008-04-01|title=PK/PD modelling and simulations: utility in drug development|journal=Drug Discovery Today|volume=13|issue=7|pages=341–346|doi=10.1016/j.drudis.2008.01.003|pmid=18405847}} and it has shown its usefulness in many diseases.{{Cite journal|last1=Karlsson|first1=Mats O.|last2=Anehall|first2=Therese|last3=Friberg|first3=Lena E.|last4=Henningsson|first4=Anja|last5=Kloft|first5=Charlotte|last6=Sandström|first6=Marie|last7=Xie|first7=Rujia|date=2005-03-01|title=Pharmacokinetic/Pharmacodynamic Modelling in Oncological Drug Development|journal=Basic & Clinical Pharmacology & Toxicology|language=en|volume=96|issue=3|pages=206–211|doi=10.1111/j.1742-7843.2005.pto960310.x|pmid=15733216|issn=1742-7843|doi-access=free}} The Food and Drug Administration also provides guidances for Industry to recommend how exposure-response studies should be performed.{{Cite web |last=Food and Drug Administration |date=2018-08-24 |title=Exposure-Response Relationships — Study Design, Data Analysis, and Regulatory Applications |url=https://www.fda.gov/regulatory-information/search-fda-guidance-documents/exposure-response-relationships-study-design-data-analysis-and-regulatory-applications |archive-url=https://web.archive.org/web/20190906034820/https://www.fda.gov/regulatory-information/search-fda-guidance-documents/exposure-response-relationships-study-design-data-analysis-and-regulatory-applications |url-status=dead |archive-date=September 6, 2019 |access-date=2022-05-09 |website=U.S. Food and Drug Administration |language=en}}

References

Category:Pharmacodynamics

Category:Pharmacokinetics