Yang Si H, Lee Myung G
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Biopharm Drug Dispos. 2008 Oct;29(7):414-26. doi: 10.1002/bdd.628.
The pharmacokinetic parameters of ondansetron were evaluated after its intravenous (at doses of 1, 4, 8 and 20 mg/kg) and oral (4, 8 and 20 mg/kg) administration to rats. The gastric, intestinal and hepatic first-pass effects of ondansetron were also evaluated after its intravenous, oral, intraportal, intragastric and intraduodenal administration at a dose of 8 mg/kg to rats. After intravenous and oral administration of ondansetron, the drug exhibits dose-independent pharmacokinetics in rats. After oral administration of ondansetron at a dose of 8 mg/kg, the unabsorbed fraction was 0.0158 of the dose, the extent of absolute oral bioavailability (F) value was 0.0407, and the hepatic and intestinal first-pass effects were 40.0% and 34.2% of the oral dose, respectively. The low F of ondansetron in rats was mainly due to considerable hepatic and intestinal first-pass effects. The lower F of ondansetron in rats (4.07%) than that in humans (62+/-15%) was mainly due to greater hepatic metabolism of the drug in rats. Ondansetron was stable in the rat gastric juices and various buffer solutions having pHs ranging from 1 to 13. The equilibrium plasma-to-blood cells partition ratio of ondansetron was 1.74-5.31. Protein binding of ondansetron to fresh rat plasma was 53.2%.
对大鼠静脉注射（剂量为1、4、8和20mg/kg）和口服（4、8和20mg/kg）昂丹司琼后，评估了其药代动力学参数。在以8mg/kg的剂量对大鼠进行静脉注射、口服、门静脉注射、胃内注射和十二指肠内注射后，还评估了昂丹司琼的胃、肠和肝首过效应。静脉注射和口服昂丹司琼后，该药物在大鼠中呈现剂量非依赖性药代动力学。口服8mg/kg剂量的昂丹司琼后，未吸收部分为给药剂量的0.0158，绝对口服生物利用度（F）值的程度为0.0407，肝和肠首过效应分别为口服剂量的40.0%和34.2%。昂丹司琼在大鼠中的低F值主要归因于显著的肝和肠首过效应。昂丹司琼在大鼠中的F值（4.07%）低于人类（62±15%），主要是因为该药物在大鼠中的肝代谢更强。昂丹司琼在大鼠胃液和pH值范围为1至13的各种缓冲溶液中稳定。昂丹司琼的血浆与血细胞平衡分配比为1.74 - 5.31。昂丹司琼与新鲜大鼠血浆的蛋白结合率为53.2%。
