Abe Fumie, Ueyama Jun, Kimata Akiko, Kato Miki, Hayashi Tamon, Nadai Masayuki, Saito Hiroko, Takeyama Naoshi, Noguchi Hiroshi, Hasegawa Takaaki
Department of Pharmacy and Pharmacokinetics, Aichi Medical University School of Medicine, Nagakute-cho, Aichi-gun, Aichi 480-1195, Japan.
Life Sci. 2008 Aug 15;83(7-8):229-35. doi: 10.1016/j.lfs.2008.06.013. Epub 2008 Jul 1.
The drug transporter, multidrug resistance-associated protein 2 (ABCC2/Mrp2), is known to play important roles in excretion of various drugs. In the present study, we investigated whether Mrp2 is involved in the transport of micafungin, a newly developed antifungal agent. When Sprague-Dawley rats received an intravenous injection of micafungin (1 mg/kg) in combination with cyclosporine, the cyclosporine significantly delayed the disappearance of micafungin from plasma and decreased the systemic clearance and volume of distribution at steady-state of micafungin to 54% and 65% of the corresponding control values, respectively. When Sprague-Dawley rats received a constant-rate infusion of micafungin, cyclosporine significantly decreased the steady-state biliary clearance of micafungin (approximately 80%). A significant decrease in the biliary clearance of micafungin (~60%) was observed in Eisai hyperbilirubinemic rats, which have a hereditary deficiency in Mrp2. The present findings at least suggest that Mrp2 is involved mainly in the hepatobiliary excretion of micafungin in rats.
药物转运体多药耐药相关蛋白2（ABCC2/Mrp2）在多种药物的排泄过程中发挥着重要作用。在本研究中，我们调查了Mrp2是否参与新型抗真菌药物米卡芬净的转运。当斯普拉格-道利大鼠静脉注射米卡芬净（1 mg/kg）并联合环孢素时，环孢素显著延迟了米卡芬净从血浆中的消失，并将米卡芬净的全身清除率和稳态分布容积分别降至相应对照值的54%和65%。当斯普拉格-道利大鼠接受米卡芬净恒速输注时，环孢素显著降低了米卡芬净的稳态胆汁清除率（约80%）。在Mrp2存在遗传性缺陷的卫材高胆红素血症大鼠中，观察到米卡芬净的胆汁清除率显著降低（约60%）。目前的研究结果至少表明，Mrp2主要参与大鼠体内米卡芬净的肝胆排泄。
