Document Detail


Basic concepts of pharmacokinetic/pharmacodynamic (PK/PD) modelling.
MedLine Citation:
PMID:  9352388     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pharmacokinetic (PK) and pharmacodynamic (PD) information from the scientific basis of modern pharmacotherapy. Pharmacokinetics describes the drug concentration-time courses in body fluids resulting from administration of a certain drug dose, pharmacodynamics the observed effect resulting from a certain drug concentration. The rationale for PK/PD-modelling is to link pharmacokinetics and pharmacodynamics in order to establish and evaluate dose-concentration-response relationships and subsequently describe and predict the effect-time courses resulting from a drug dose. Under pharmacokinetic steady-state conditions, concentration-effect relationships can be described by several relatively simple pharmacodynamic models, which comprise the fixed effect model, the linear model, the long-linear model, the Emax-model and the sigmoid Emax-model. Under non steady-state conditions, more complex integrated PK/PD-models are necessary to link and account for a possible temporal dissociation between the plasma concentration and the observed effect. Four basic attributes may be used to characterize PK/PD-models: First, the link between measured concentration and the pharmacologic response mechanism that mediates the observed effect, direct vs. indirect link; second, the response mechanism that mediates the observed effect, direct vs. indirect response; third, the information used to establish the link between measured concentration and observed effect, hard vs. soft link; and fourth, the time dependency of the involved pharmacodynamic parameters, time-variant vs. time-invariant. In general, PK/PD-modelling based on the underlying physiological process should be preferred whenever possible. The expanded use of PK/PD-modelling is assumed to be highly beneficial for drug development as well as applied pharmacotherapy and will most likely improve the current state of applied therapeutics.
Authors:
B Meibohm; H Derendorf
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  International journal of clinical pharmacology and therapeutics     Volume:  35     ISSN:  0946-1965     ISO Abbreviation:  Int J Clin Pharmacol Ther     Publication Date:  1997 Oct 
Date Detail:
Created Date:  1998-02-05     Completed Date:  1998-02-05     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  9423309     Medline TA:  Int J Clin Pharmacol Ther     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  401-13     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville 32610, USA.
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MeSH Terms
Descriptor/Qualifier:
Dose-Response Relationship, Drug
Drug Tolerance
Forecasting
Humans
Linear Models
Models, Biological*
Pharmacokinetics*
Pharmacology / trends*

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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