Intestinal Absorption and Hepatic Extraction of Propranolol and Metoprolol in Rats with Bilateral Ureteral Ligation(Biopharmacy)
スポンサーリンク
概要
- 論文の詳細を見る
To investigate the mechanism responsible for the increased bioavailability of propranolol in bilateral ureterligated (BUL) rats, the intestinal absorption and hepatic extraction of propranolol and metoprolol were evaluated. The initial absorption rate of these drugs after intra-intestinal administration was only slightly increased in the BUL rats, whereas the blood drug concentration in these rats was higher than that in control rats. The blood propranolol and metoprolol concentrations during intra-portal infusion in the BUL rat were significantly higher than that in the control rat. In the presence of NADPH, the intrinsic metabolic activity of metoprolol in hepatic microsomes was not altered by BUL. On the other hand, the NADPH generation rate in the hepatic cytosol in the BUL group was lower than that in the control group. These results indicate that the absorption rate-dependent decrease in hepatic first-pass clearance of propranolol and metoprolol due to saturation kinetics is marginal, and that the hepatic metabolic activity and extraction of the drugs is significantly decreased in BUL rats probably due to the reduced NADPH generation rate in the liver.
- 公益社団法人日本薬学会の論文
- 2004-09-01
著者
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HASHIMOTO Yukiya
Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University
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OKABE Hiromi
Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University
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Okabe Hiromi
Graduate School Of Pharmaceutical Sciences Toyama Medical And Pharmaceutical University
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Hashimoto Yukiya
Graduate School Of Medicine And Pharmaceutical Sciences Univ. Of Toyama
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HIGASHI Takashi
Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University
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OHTA Takako
Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University
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Higashi Takashi
富山医科薬科大学 薬学研究科
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Higashi Takashi
Graduate School Of Pharmaceutical Sciences Toyama Medical And Pharmaceutical University
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Ohta Takako
Graduate School Of Engineering Doshisha University
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Ohta Takako
Graduate School Of Pharmaceutical Sciences Toyama Medical And Pharmaceutical University
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Higashi Takashi
Graduate School Of Pharmaceutical Sciences Toyama Medical And Pharmaceutical Univ.
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