Pharmacokinetics and Hepatic Extraction of Metoprolol in Rats with Glycerol-Induced Acute Renal Failure(Biopharmacy)

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概要

• 論文の詳細を見る

• The aim of the present study was to evaluate the effect of glycerol-induced acute renal failure (ARF) on the pharmacokinetics and hepatic extraction of metoprolol in rats. Experimental ARF in rats was induced by injections of 50% glycerol into the leg muscle (10 ml/kg). Pharmacokinetics and hepatic extraction of metoprolol was evaluated by means of intravenous, intra-intestinal, and intra-portal administration of the drug. The blood metoprolol concentration following intravenous infusion in ARF rats was similar to that in control rats. On the other hand, the blood metoprolol concentration at 5-10 min after intra-intestinal administration in ARF rats was significantly higher than that in control rats, and the oral clearance (CL/F) of the drug was significantly decreased in ARF rats. Hepatic extraction following intra-portal infusion was not altered by glycerol-induced ARF; however, hepatic first-pass extraction of metoprolol was dose-dependent and saturable in both ARF and control rats. These results suggested that the decreased CL/F of metoprolol in rats with glycerol-induced ARF is mainly a result of the increased initial absorption rate in the intestine followed by partial saturation of hepatic first-pass metabolism.

• 公益社団法人日本薬学会の論文
• 2007-03-01

著者

• TAGUCHI Masato

  Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University

• HASHIMOTO Yukiya

  Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University

• Hashimoto Y

  Graduate School Of Pharmaceutical Sciences Kyushu University

• Hashimoto Yuichi

  Institute Of Molecular & Cellular Biosciences University Of Tokyo

• Tanabe Hiroko

  Graduate School Of Pharmaceutical Sciences University Of Toyama

• Harada Yuichi

  Center For Influenza Virus Research National Institute Of Infectious Diseases

• Taguchi Masato

  Graduate School Of Medicine And Pharmaceutical Sciences Univ. Of Toyama

• Hashimoto Yukiya

  Graduate School Of Medicine And Pharmaceutical Sciences Univ. Of Toyama

• TAIRA Shigehiro

  Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama

• Taira Shigehiro

  Graduate School Of Medicine And Pharmaceutical Sciences University Of Toyama

• Hashimoto Y

  Institute Of Molecular & Cellular Biosciences The University Of Tokyo

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