The in-vitro metabolism of [14C]pentobarbitone and [14C]phenobarbitone by hamster liver microsomes.
The metabolism of [14C]pentobarbitone and [14C]phenobarbitone has been reinvestigated using an in-vitro hepatic microsomal system (Syrian hamsters, Aroclor 1254 induction). The incubation system was routinely supplemented with EDTA (1 mM) and a substrate concentration study revealed the metabolism of [14C]pentobarbitone to be concentration-dependent, with the greatest overall metabolism (greater than 50%) occurring at 0.054 mumol per 3.5 mL. With [14C]phenobarbitone as substrate, overall metabolism was extremely low (3%) and independent of substrate concentration. Addition of further cofactors to the incubation mixture at 20 min intervals over an extended period resulted in almost complete metabolism of [14C]pentobarbitone (100 min), 3'-hydroxypentobarbitone and 3'-oxopentobarbitone being identified as metabolites together with many minor, unidentified products. With [14C]phenobarbitone as the substrate, cofactor addition up to 120 min resulted in 8% overall metabolism; p-hydroxyphenobarbitone was identified as a product of metabolism; other minor products were unidentified. The metabolism studies failed to produce a metabolite having the properties of the N-hydroxylated product of either [14C]pentobarbitone or [14C]phenobarbitone within the detection limits available (0.02% of 0.5 mumol per incubate).
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D002250:Carbon Radioisotopes; D020111:Chlorodiphenyl (54% Chlorine); D006224:Cricetinae; D006877:Hydroxamic Acids / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010424:Pentobarbital / Q000378:metabolism* / Q000494:pharmacology; D010634:Phenobarbital / Q000378:metabolism* / Q000494:pharmacology
D001140:Aroclors; D002250:Carbon Radioisotopes; D006877:Hydroxamic Acids; D020111:Chlorodiphenyl (54% Chlorine); D010424:Pentobarbital; D010634:Phenobarbital