Drew R, Priestly B G, O'Reilly W J
J Pharmacol Exp Ther. 1977 Jun;201(3):534-40.
Rats, with and without bile duct ligation (BDL), were injected with hexobarbital (i.p. and i.v.) and blood concentrations measured as a function of time. Analysis of these curves using a single-compartment model showed that BDL altered hexobarbital pharmacokinetics in a manner dependent upon the duration of BDL and the route of administration of hexobarbital. Clearance from the blood and the rate constant for elimination (K) were reduced after 72-hour BDL but not after 12-hour BDL. The absorption of hexobarbital after intraperitoneal injection was slowed by 12- and 72- hour BDL. Seventy-two-hour BDL also increased the volume of distribution of hexobarbital but only when the drug was administered intraperitoneally. These data are consistent with previously reported data showing impairment of hepatic microsomal drug metabolism after 72-hour BDL, but not after 12-hour BDL. We also confirmed earlier speculations that BDL decreased the absorption of intraperitoneally-administered hexobarbital, although this does not appear to be a significant factor in prolonging hexobarbital sleeping time.
对有和没有进行胆管结扎（BDL）的大鼠腹腔注射和静脉注射己巴比妥，并测定其血药浓度随时间的变化。使用单室模型对这些曲线进行分析，结果显示BDL会改变己巴比妥的药代动力学，其改变方式取决于BDL的持续时间以及己巴比妥的给药途径。在进行72小时BDL后，血液清除率和消除速率常数（K）降低，但12小时BDL后未出现这种情况。12小时和72小时BDL均会减慢腹腔注射后己巴比妥的吸收。72小时BDL还会增加己巴比妥的分布容积，但仅在药物经腹腔给药时出现这种情况。这些数据与之前报道的显示72小时BDL后肝微粒体药物代谢受损、12小时BDL后未受损的数据一致。我们还证实了之前的推测，即BDL会降低腹腔注射己巴比妥的吸收，尽管这似乎不是延长己巴比妥睡眠时间的重要因素。
