Effects of chronic treatment with amiodarone on hepatic demethylation and cytochrome P450.
The effect of chronic treatment with amiodarone on hepatic oxidative metabolism using an in-vivo [14C]aminopyrine breath test and on hepatic cytochrome P450 was examined in Wistar rats. Aminopyrine demethylation was significantly impaired but returned to pretreatment values following amiodarone for 4 weeks. In contrast the levels of cytochrome P450 were significantly depressed during treatment and at 4 weeks following treatment. While an inhibitory effect on oxidative metabolism may explain the reported drug interactions with amiodarone, the discrepancy between its in-vivo effects and cytochrome P450 levels may suggest the development of 'compensatory' extra-hepatic site of drug metabolism.
D000375:Aging / Q000378:metabolism; D000632:Aminopyrine / Q000378:metabolism; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003640:Dealkylation; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000632:Aminopyrine; D003577:Cytochrome P-450 Enzyme System; D000638:Amiodarone