Bae Soo K, Kim Jin W, Kim Young H, Kim Yoon G, Kim Sang G, Lee Myung G
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, Republic of Korea.
Biopharm Drug Dispos. 2005 May;26(4):129-34. doi: 10.1002/bdd.439.
It was reported that the mean value of the extent of absolute oral bioavailability (F) of oltipraz at a dose of 20 mg/kg was 41.2% and only 2.68% of the oral dose was unabsorbed from the gastrointestinal tract in rats. Hence, the low F in rats could be due to considerable first-pass (gastric, intestinal and hepatic) effects. Hence, the first-pass effects of oltipraz were measured after intravenous, intraportal, intragastric and intraduodenal administration of the drug at a dose of 20 mg/kg to rats. The total area under the plasma concentration-time curve from time zero to time infinity (AUC) values between intragastric and intraduodenal administration (213 and 212 microg min/ml) in rats were almost similar, but the values were significantly smaller than that after intraportal administration (316 microg min/ml) in rats, indicating that gastric first-pass effect was almost negligible (due to negligible absorption of oltipraz from rat stomach), but the intestinal first-pass effect of oltipraz was considerable, approximately 32% of the oral dose. The hepatic first-pass effect of oltipraz was approximately 40% based on AUC values between intravenous and intraportal administration (319 versus 536 microg min/ml). Since approximately 65% of the oral oltipraz was absorbed into the portal vein, the value of 40% was equivalent to 25% of the oral dose. The low F of oltipraz in rats was mainly due to considerable hepatic and intestinal first-pass effects.
据报道，在大鼠中，20mg/kg剂量的奥替普拉绝对口服生物利用度（F）的平均值为41.2%，口服剂量中仅有2.68%未从胃肠道吸收。因此，大鼠中F值较低可能是由于显著的首过效应（胃、肠道和肝脏）。因此，在给大鼠静脉注射、门静脉注射、胃内注射和十二指肠内注射20mg/kg剂量的该药物后，测定了奥替普拉的首过效应。大鼠胃内注射和十二指肠内注射后的血浆浓度-时间曲线从零到无穷大的总面积（AUC）值（213和212μg·min/ml）几乎相似，但这些值显著小于大鼠门静脉注射后的AUC值（316μg·min/ml），表明胃首过效应几乎可以忽略不计（由于奥替普拉从大鼠胃中的吸收可忽略不计），但奥替普拉的肠道首过效应相当大，约为口服剂量的32%。基于静脉注射和门静脉注射后的AUC值（319对536μg·min/ml），奥替普拉的肝脏首过效应约为40%。由于口服奥替普拉约65%被吸收进入门静脉，40%的值相当于口服剂量的25%。大鼠中奥替普拉的F值较低主要是由于显著的肝脏和肠道首过效应。
