Wang Zhe, Wang Li, Xia Meng-Ming, Sun Wei, Huang Cheng-Ke, Cui Xiao, Hu Guo-Xin, Lian Qing-Quan, Wang Zeng-Shou
Department of Pharmacy, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, China.
Biomed Res Int. 2015;2015:368976. doi: 10.1155/2015/368976. Epub 2015 Jan 5.
The objective of this work was to investigate the effect of orally administered genistein on the pharmacokinetics of imatinib and N-desmethyl imatinib in rats. Twenty-five healthy male SD (Sprague-Dawley) rats were randomly divided into five groups: A group (control group), B group (multiple dose of 100 mg/kg genistein for consecutive 15 days), C group (multiple dose of 50 mg/kg genistein for consecutive 15 days), D group (a single dose of 100 mg/kg genistein), and E group (a single dose of 50 mg/kg genistein). A single dose of imatinib is administered orally 30 min after administration of genistein (100 mg/kg or 50 mg/kg). The pharmacokinetic parameters of imatinib and N-desmethyl imatinib were calculated by DAS 3.0 software. The multiple dose of 100 mg/kg or 50 mg/kg genistein significantly (P < 0.05) decreased the AUC0-t and C max of imatinib. AUC0-t and the C max of N-desmethyl imatinib were also increased, but without any significant difference. However, the single dose of 100 mg/kg or 50 mg/kg genistein has no effect on the pharmacokinetics of imatinib and N-desmethyl imatinib. Those results indicated that multiple dose of genistein (100 mg/kg or 50 mg/kg) induces the metabolism of imatinib, while single dose of genistein has no effect.
本研究旨在探讨口服染料木黄酮对大鼠体内伊马替尼及其N-去甲基代谢产物药代动力学的影响。将25只健康雄性SD（Sprague-Dawley）大鼠随机分为五组：A组（对照组）、B组（连续15天每日多次给予100 mg/kg染料木黄酮）、C组（连续15天每日多次给予50 mg/kg染料木黄酮）、D组（单次给予100 mg/kg染料木黄酮）和E组（单次给予50 mg/kg染料木黄酮）。在给予染料木黄酮（100 mg/kg或50 mg/kg）30分钟后，口服单次剂量的伊马替尼。采用DAS 3.0软件计算伊马替尼及其N-去甲基代谢产物的药代动力学参数。多次给予100 mg/kg或50 mg/kg染料木黄酮可显著（P < 0.05）降低伊马替尼的AUC0-t和Cmax。N-去甲基伊马替尼的AUC0-t和Cmax也有所升高，但无显著差异。然而，单次给予100 mg/kg或50 mg/kg染料木黄酮对伊马替尼及其N-去甲基代谢产物的药代动力学无影响。这些结果表明，多次给予染料木黄酮（100 mg/kg或50 mg/kg）可诱导伊马替尼的代谢，而单次给予则无此作用。
