Richter E, Gallenkamp H, Brachtel D, Grün M
Z Gastroenterol. 1977 Jun;15(6):389-92.
Male rats were pretreated with phenobarbital for 5 days or received portacaval anastomosis 3 weeks before. Hexobarbital was applicated intravenously and hexobarbital plasma concentrations were followed up gaschromatographically in arterial blood samples. Hexobarbital clearance was calculated from the plasma concentration curve versus time. Liver microsomes were prepared and cytochrome P 450 and the hexobarbital oxidation rate was determined. After portacaval shunt the animals showed a small liver, a reduced cytochrome P 450 and diminished hexobarbital oxidation rate. Hexobarbital clearance in vivo was reduced, too. After phenobarbital pretreatment liver weight increased and cytochrome P 450 and hexobarbital oxidation rate were distinctly enhanced. The hexobarbital clearance in vivo were increased. Since the plot of hexobarbital clearance in vivo versus cytochrome P 450 or versus hexobarbital oxidation rate in vitro gave a good correlation, it is concluded that hexobarbital clearance in vivo may be a good estimate for hepatic cytochrome P 450 and hepatic hexobarbital oxidation rate.
雄性大鼠先接受苯巴比妥预处理5天,或在3周前进行门腔静脉吻合术。静脉注射己巴比妥,并通过气相色谱法对动脉血样本中的己巴比妥血浆浓度进行跟踪监测。根据血浆浓度曲线随时间的变化计算己巴比妥清除率。制备肝微粒体并测定细胞色素P450和己巴比妥氧化率。门腔静脉分流术后,动物肝脏变小,细胞色素P450减少,己巴比妥氧化率降低。体内己巴比妥清除率也降低。苯巴比妥预处理后,肝脏重量增加,细胞色素P450和己巴比妥氧化率明显提高。体内己巴比妥清除率增加。由于体内己巴比妥清除率与细胞色素P450或体外己巴比妥氧化率的关系图具有良好的相关性,因此得出结论:体内己巴比妥清除率可能是肝细胞色素P450和肝脏己巴比妥氧化率的良好估计指标。