Seago A, Gorrod J W
J Pharm Pharmacol. 1987 Feb;39(2):84-9. doi: 10.1111/j.2042-7158.1987.tb06950.x.
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).
已使用体外肝微粒体系统（叙利亚仓鼠，用多氯联苯混合物Aroclor 1254诱导）对[14C]戊巴比妥和[14C]苯巴比妥的代谢进行了重新研究。孵育系统常规添加乙二胺四乙酸（1 mM），底物浓度研究表明[14C]戊巴比妥的代谢呈浓度依赖性，每3.5 mL中0.054 μmol时总体代谢最高（超过50%）。以[14C]苯巴比妥为底物时，总体代谢极低（3%）且与底物浓度无关。在较长时间内每隔20分钟向孵育混合物中添加其他辅因子，导致[14C]戊巴比妥几乎完全代谢（100分钟），鉴定出3'-羟基戊巴比妥和3'-氧代戊巴比妥为代谢产物，还有许多少量未鉴定产物。以[14C]苯巴比妥为底物时，添加辅因子至120分钟导致总体代谢为8%；对羟基苯巴比妥被鉴定为代谢产物；其他少量产物未鉴定。在可用的检测限内（每孵育0.5 μmol的0.02%），代谢研究未能产生具有[14C]戊巴比妥或[14C]苯巴比妥N-羟基化产物特性的代谢物。
