Gender differences in ondansetron pharmacokinetics in rats
Gender differences in ondansetron pharmacokinetics in rats
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DOI：
10.1002/bdd.627
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发表时间：
2008-10
影响因子：
2.1
通讯作者：
Si-hyung Yang;Kyung H. Yang;Myung G. Lee
中科院分区：
文献类型：
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作者：
Si-hyung Yang;Kyung H. Yang;Myung G. Lee
据报道，在雄性Sprague-Dawley大鼠中，昂丹司琼主要通过肝脏CYP 2D和3A 1/2代谢，CYP 2D 1和3A 2分别是雄性优势和雄性特异性同工酶。因此，可以预期昂丹司琼在雄性大鼠中的药代动力学与在雌性大鼠中的药代动力学相比会发生变化。因此，以8 mg/kg剂量静脉或经口给予雄性和雌性Sprague-Dawley大鼠后，评价了性别差异的昂丹司琼药代动力学。雄性大鼠静脉给予昂丹司琼后，药物的AUC和时间平均非肾清除率（Clnr）分别显著小于（降低22.6%）和快于（增加27.3%）雌性大鼠。这可能是由于雄性大鼠的肝血流速度更快。雄性大鼠经口给予昂丹司琼后，药物的AUC也显著小于雌性大鼠（降低58.8%），这可能主要是由于雄性大鼠中昂丹司琼的肠道代谢增加以及药物的肝脏代谢增加所致。版权所有© 2008约翰威利父子有限公司。
It has been reported that ondansetron is primarily metabolized via hepatic CYP2D and 3A1/2 in male Sprague–Dawley rats, and CYP2D1 and 3A2 are male dominant and male specific isozymes, respectively, in rats. Thus, it could be expected that the pharmacokinetics of ondansetron would be changed in male rats compared with those in female rats. Thus, gender‐different ondansetron pharmacokinetics were evaluated after its intravenous or oral administration at a dose of 8 mg/kg to male and female Sprague–Dawley rats. After intravenous administration of ondansetron to male rats, the AUC and time‐averaged non‐renal clearance (Clnr) of the drug were significantly smaller (22.6% decrease) and faster (27.3% increase), respectively, than those in female rats. This probably could be due to faster hepatic blood flow rate in male rats. After oral administration of ondansetron to male rats, the AUC of the drug was also significantly smaller (58.8% decrease) than that in female rats, and this could have been due mainly to increased intestinal metabolism of ondansetron in addition to increased hepatic metabolism of the drug in male rats. Copyright © 2008 John Wiley & Sons, Ltd.