Contrasting effect of isoflurane on drug metabolism: decreased type I and increased type II substrate metabolism in guinea pig liver microsomes.

Journal of applied toxicology : JAT

PubMedID: 8854220

Rahman MM, Fujii K, Kawamoto M, Yuge O. Contrasting effect of isoflurane on drug metabolism: decreased type I and increased type II substrate metabolism in guinea pig liver microsomes. J Appl Toxicol. 1997;16(4):331-7.
Inhalation anaesthetics might affect perioperative drug elimination by altering drug distribution, hepatic blood flow or drug metabolism. The in vitro effects of isoflurane on aniline hydroxylation and aminopyrine N-demethylation were investigated with guinea pig liver microsomes to assess the role of isoflurane on oxidative drug metabolism through the hepatic mixed-function oxidase system. p-Aminophenol and formaldehyde were measured spectrophotometrically as metabolic products of aniline hydroxylation and aminopyrine N-demethylation, respectively, where the reaction mixture consisted of a microsomal suspension, NADPH, aminopyrine or aniline, with or without isoflurane. The rate of cytochrome P-450 reduction by NADPH affected in the presence of isoflurane was investigated by spectrometric measurement of the CO-cytochrome P-450 complex formation at various times. Due to the addition of isoflurane, the Vmax values for aniline hydroxylation evidently increased except in high isoflurane concentration (3.33 mM) and for aminopyrine N-demethylation the value was significantly low only in the presence of a high isoflurane concentration, whereas the K(m) values significantly decreased in aniline hydroxylation and increased in aminopyrine N-demethylation, and isoflurane also accelerated the rate of cytochrome P-450 reduction by NADPH. These results reflect the inhibition of aminopyrine N-demethylation and activation of aniline hydroxylation in the presence of isoflurane as a consequence of isoflurane-accelerated cytochrome P-450 reduction by NADPH and/or drug-enzyme binding properties, and may have implications on the metabolism of perioperatively administered drugs during isoflurane anaesthesia.