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| 題名: | Measurement of unbound ranitidine in blood and bile of anesthetized rats using microdialysis coupled to liquid chromatography and its pharmacokinetic application |
| 作者: | Huang, SM;Tsai, TR;Yeh, PH;Tsai, TH |
| 貢獻者: | 中醫學院中醫所
Natl Yang Ming Univ, Inst Tradit Med, Taipei, Taiwan;Natl Yang Ming Univ, Inst Pharmacol, Taipei, Taiwan;Kaohsiung Med Univ, Fac Pharm, Kaohsiung 807, Taiwan;China Med Univ, Grad Inst Chinese Med Sci, Taichung, Taiwan;Natl Res Inst Chinese Med, Dept Pharmacol, Taipei 112, Taiwan |
| 日期: | 2005 |
| 上傳時間: | 2010-09-20 13:44:13 (UTC+8) |
| 出版者: | ELSEVIER SCIENCE BV |
| 摘要: | To investigate the pharmacokinetics of unbound ranitidine in rat blood and bile, multiple microdialysis probes coupled to a liquid chromatographic system were developed. This study design was parallel in the following groups: the control-group of six rats received ranitidine alone (10 and 30 mg/kg. i.v.), the treated-group rats were co-administered with ranitidine and cyclosporine (P-glycoprotein (P-gp) inhibitor) or quinidine (both organic cation transport (OCT) and P-gp inhibitors) in six individual rats. Microdialysis probes were inserted into the jugular vein and the bile duct for blood and bile fluids sampling, respectively. Ranitidine in the dialysate was separated by a reversed-phase C-18 column (Zorbax. 150 mm x 4.6 mm i.d.; 5 μ m) maintained at ambient temperature. Samples were eluted with a mobile phase containing acetonitrile-methanol-tetrahydrofuran-20 mM K2HPO4 (pH 7.0) (24:20:10:946, v/v), and the flow rate of the mobile phase was 1 ml/min. The optimal UV detection for ranitidine was set at wavelength 315 nm. Between 20 and 30 min after drug administration (10 or 30 mg/kg), the ranitidine reached the maximum concentration in the bile. The bile-to-blood distribution ratio (AUC(bile)/AUC(blood)) was 9.8 ± 1.9 and 13.9 ± 3.8 at the dosages of 10 and 30mg/kg, respectively. These studies indicate that ranitidine undergoes hepatobiliary excretion which against concentration gradient from bile-to-blood. In addition, the AUC of ranitidine in bile decreased in the treatment of cyclosporine or quinidine, which suggests that the hepatobiliary excretion of ranitidine was partially regulated by P-glycoprotein or organic cation transporter. © 2004 Elsevier B.V. All rights reserved. |
| 關聯: | JOURNAL OF CHROMATOGRAPHY A 1073(1月2日):297-302 |
| 顯示於類別: | [中國醫學研究所] 會議論文
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