تداخل برخي از داروهاي فنوتيازيني با متابوليسم فمسايكلو وير توسط آلدييداكسيد از كبد خوكچه هندي INVITOR بررسي

In vitro study of interaction of some phenothiazines and purines with famciclovir metabolism catalyzed by guinea pig liver aldehyde oxidase

Famciclovir is a guanosine nucleoside analogue with activity against herpes viruses and hepatitis B virus. Following oral administration, famciclovir is rapidly hydrolyzed to 6-deoxypenciclovir which undergoes extensive oxidation to penciclovir. In vitro studies have shown that both famciclovir and 6-deoxypenciclovir serve as substrates for hepatic aldehyde oxidase. Thus, it would be likely that those compounds that act as aldehyde oxidase inhibitors/substrates interfere with penciclovir formation. In the present in vitro study, the possible interaction of some phenothiazines and purins with the metabolism of famciclovir is investigated. Aldehyde oxidase was partially purified from guinea pig liver and the interaction of chloepromazine, promethazine, phenothiazine, azathioprine, 6-mercaptopurine, theophylline, caffeine and allopurinol with famciclovir or 6-deoxypenciclovir oxidation was investigated using spectrophotometric or HPLC methods. Only phenothizines caused marked inhibition on both oxidations with chlorpromazine giving the highest inhibition. The oxidation of famciclovir or 6-deoxypenciclovir was not significantely affected by allopurinol (the xanthine oxidase inhibitor) confirming that aldehyde oxidase, not xanthine oxidase, is the major molybdenum hydroxylase in the oxidation of both substrates in guinea pig liver fractions.