Valproic Acid Elimination Rate and Urinary Excretion of Its Glucuronide Conjugate in Patients with Epilepsy

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概要

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• We previously encountered a patient with epilepsy who exhibited rapid elimination of sustained-release valproic acid (VPA) administered at the dose of 2.8 g/d as a sodium salt. The purpose of this study was to clarify the relationship between the VPA elimination rate and the proportion of the dose excreted in urine as its glucuronide conjugate (VPA-G) in epileptic patients. Twenty-four-hour urine was collected from four epileptic patients who had taken VPA orally (age : 16-39y, weight : 50-63 kg, dose : 1.0-2.8 g/d). VPA and its metabolites were detected by gas chromatography-mass spectrometry. The amounts of VPA, VPA-G, 3-keto VPA, and 3-OH VPA excreted in the 24-h urine were 1.8-13.2,178-2158,125-320,and 8.6-18.7 mg (converted into VPA), respectively, and 0.2-0.5,20.5-88.7,5.8-18.7,and 0.6-1.0% of the dose administered, respectively. The dose of VPA correlated well with the proportion of the dose excreted in urine as VPA-G in each patient, and the patients administered a high dose excreted a large amount of VPA-G in the urine. Thus, differences in the VPA-G production rate may be one of the major variable factors affecting the elimination of administered VPA. We also present a dynamic model of VPA in the kidney which may explain the VPA elimination phenomena in humans on the basis of the data obtained here regarding the concentrations of VPA and its metabolites in plasma and their urinary excretion levels.

• 社団法人日本薬学会の論文
• 1999-07-15

著者

• 渡辺 光男

  Hamamatsu Photonics K. K.

• KAMIYA Akira

  Department of Pharmacy, Yamaguchi University Hospital

• HISHINUMA TAKANORI

  Division of Pharmacotherapy, Graduate School of Pharmaceutical Sciences, Tohoku University

• Kamiya A

  Department Of Pharmacy Yamaguchi University Hospital

• Kamiya Akira

  Department Of Pharmacy Yamaguchi University Hospital

• YOSHITOMI Hironori

  Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University

• YOSHIDA Hisahiro

  Department of Drug Metabolism and Disposition, Meiji Pharmaceutical University

• Yoshida H

  Department Of Pharmacy Yamaguchi University Hospital

• Yoshida H

  Yamaguchi Univ. Hospital Yamaguchi Jpn

• Yoshida Hisahiro

  Department Of Drug Metabolism And Disposition Meiji Pharmaceutical University

• Watanabe M

  Faculty Of Pharmacy And Pharmaceutical Sciences Fukuyama University

• HIROZANE Kiyoshi

  Department of Pharmacy, Yamaguchi University Hospital

• KIMOTO Hiroo

  Department of Pharmacy, Yamaguchi University Hospital

• HAYASHI Takasi

  Department of Pediatrics, Yamaguchi University School of Medicine

• AKIYAMA Tatsuo

  Department of Neurosurgery, Yamaguchi University School of Medicine

• KATAYAMA Hirokazu

  Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University

• WATANABE Miki

  Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University

• Kamiya Akira

  Department Of Biomedical Engineering University Of Tokyo

• Katayama H

  Fukuyama Univ. Hiroshima Jpn

• Hayashi T

  Department Of Pharmacy Fujita Health University Hospital

• Watanabe M

  Department Of Public Health Niigata College Of Medical Technology

• AKIYAMA Toshihiko

  Faculty of Pharmaceutical Sciences, Okayama University

• Akimura T

  Department Of Neurosurgery Yamaguchi University School Of Medicine

• Yoshitomi Hironori

  Faculty Of Pharmaceutical Sciences Okayama University

• Akiyama T

  Faculty Of Pharmaceutical Sciences Okayama University

• Kimoto H

  Department Of Pharmacy Yamaguchi University Hospital

• Kimoto Hiroo

  Department Of Pathology Wakayama Medical College

• Katayama Hirokazu

  Faculty Of Pharmacy And Pharmaceutical Sciences Fukuyama University

• Hishinuma T

  Division Of Clinical Pharmacy Graduate School Of Pharmaceutical Sciences Tohoku University

• Hirozane Kiyoshi

  Department Of Pharmacy Yamaguchi University Hospital

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