Methods for studying the hepatic metabolism of drugs in man
Geneve, J.; Bergmann, J.F.; Caulin, C.; Segrestaa, J.M.
Therapie 45(2): 91-97
1990
ISSN/ISBN: 0040-5957 PMID: 2191470 Document Number: 356931
Various methods can be used to investigate human hepatic drug metabolism in vivo. a) Indirect methods based on the assessment of atoxic substances metabolism in order to investigate: --hepatic oxidative activity by antipyrine or caffeine clearance and aminopyrine breath test determination. Such an activity can be modified by drug-induced enzyme induction or inhibition and in case of hepatic disease; --genetic polymorphism of hepatic drug metabolism assessed by the determination of debrisoquine or dextrometorphane metabolic ratio and of N-acetylation phénotype. Unusual therapeutic or adverse effects could be explained by such a polymorphism; --hepatic blood flow, which variations could modify hepatic clearance of drugs with a high hepatic extraction ratio, by the assessment of indocyanine green clearance. b) Direct methods based on pharmacokinetics data and their alterations under various circumstances: simultaneous administration of other drugs, liver disease.