Effects of perphenazine, diazepam and nitrazepam on amitriptyline metabolism in rat.
Repeated coadministration of amitriptyline (AMT) and perphenazine (PPZ) decreased the AMT-induced increase of hepatic microsomal aminopyrine N-demethylase, aniline hydroxylase, NADPH-cytochrome c reductase and UDP-glucuronyltransferase (UDP-GT) activities in rats. This may be explained by a fact that inhibition of AMT metabolism in hepatic microsomes by PPZ led to increase the non-conjugated formation of AMT and its metabolites in the liver, brain, urine and feces. On the other hand, a slight decrease of drug metabolizing enzyme activity by diazepam (DZP) but not by nitrazepam (NTZ) was enhanced by combined treatment of AMT, whereas the enhancement of UDP-GT activity by DZP or NTZ was suppressed by coadministration of AMT. At the same time there was no clear increase of non-conjugated formation of AMT metabolites in rat urine and feces during combined treatment.
D000639:Amitriptyline / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000032:analysis; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009567:Nitrazepam / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010546:Perphenazine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013466:Sulfurtransferases / Q000032:analysis
D000639:Amitriptyline; D009567:Nitrazepam; D014453:Glucuronosyltransferase; D013466:Sulfurtransferases; D010546:Perphenazine; D003975:Diazepam