The Determination of Drug Metabolizing Enzyme Activity In Vivo: Pharmacokinetics and Statistical Issues

Probe substrates for various isoforms of cytochrome P450 and other drug-metabolizing enzymes are now widely used to assess genetic, environmental and ethnic differences in the in vivo metabolism of drugs and other xenobiotics .The key issues in assessing drug-metabolizing enzyme activity in vivo include separation (with the aid of genotyping) of risk and exposure; choice of the best experimental index to use, the selection and number of subjects for study, and the use of objective criteria for assessing multimodality in frequency distributions of in vivo data .To avoid misinterpretation and overinterpretation of data, it is essential to have a good understanding of the pharmacokinetic basis of indirect measures of in vivo drug-metabolizing activity, and of appropriate statistical procedures for the analysis of frequency distributions.

 

Author(s): Geoffrey Tucker, Amin Rostami-Hodjegan, Peter Jackson

Year: December 1, 1998

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