Repository of Research and Investigative Information

Repository of Research and Investigative Information

Ahvaz Jundishapur University of Medical Sciences

Incorporating in vitro information on drug metabolism into clinical trial simulations to assess the effect of CYP2D6 polymorphism on pharmacokinetics and pharmacodynamics: Dextromethorphan as a model application

Dickinson, G. L. and Rezaee, S. and Proctor, N. J. and Lennard, M. S. and Tucker, G. T. and Rostami-Hodjegan, A. (2007) Incorporating in vitro information on drug metabolism into clinical trial simulations to assess the effect of CYP2D6 polymorphism on pharmacokinetics and pharmacodynamics: Dextromethorphan as a model application. Journal of Clinical Pharmacology, 47 (2). pp. 175-186. ISSN 00912700 (ISSN)

Full text not available from this repository.
Official URL: https://www.scopus.com/inward/record.uri?eid=2-s2....

Abstract

In vitro-in vivo extrapolation of clearance, embedded in a clinical trial simulation, was used to investigate differences in the pharmacokinetics and pharmacodynamics of dextromethorphan between CYP2D6 poor and extensive metabolizer phenotypes. Information on the genetic variation of CYP2D6, as well as the in vitro metabolism and pharmacodynamics of dextromethorphan and its active metabolite dextrorphan, was integrated to assess the power of studies to detect differences between phenotypes. Whereas 6 subjects of each phenotype were adequate to achieve 80 power in showing pharmacokinetic differences, the power required to detect a difference in antitussive response was less than 80 with 500 subjects in each study arm. Combining in vitro-in vivo extrapolation with a clinical trial simulation is useful in assessing different elements of study design and could be used a priori to avoid inconclusive pharmacogenetic studies. ©2007 the American College of Clinical Pharmacology.

Item Type: Article
Keywords: Clinical trial simulation Cytochrome P450 In silico Pharmacogenetics Polymorphic drug metabolism antitussive agent cytochrome P450 2D6 dextromethorphan dextrorphan article drug activity drug clearance drug effect drug metabolism drug response enzyme polymorphism genetic variability in vitro study in vivo study phenotype simulation Antitussive Agents Clinical Trials Computer Simulation Cough Cytochrome P-450 CYP2D6 Models, Biological Polymorphism, Genetic
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine, Health and Life Sciences
Depositing User: مهندس مهدی شریفی
Last Modified: 01 Jun 2018 13:14
URI: http://eprints.ajums.ac.ir/id/eprint/19568

Actions (login required)

View Item View Item