Pharmacokinetics and Metabolism of an α,β-Blocker, Amosulalol Hydrochloride, in Mice : Biliary Excretion of Carbamoyl Glucuronide(Biopharmacy)

スポンサーリンク

概要

• 論文の詳細を見る

• The pharmacokinetics and metabolism of an α,β-blocker, amosulalol hydrochloride, were investigated in mice. After intravenous administration (10 mg/kg), the plasma concentration of the unchanged drug declined biphasically, with a terminal half-life of 1.1 h. The maximum plasma concentrations were reached at 0.25 h after oral administration, and then declined with apparent half-lives of 0.8-1.3 h. The systemic bioavailability of a 10-mg/kg dose was 38.7%. The area under the plasma concentration curve increased more than proportionally to the dose, which suggests metabolic saturation. After oral and intravenous administrations of ^<14>C-labelled amosulalol hydrochloride, 64.7% and 81.0% of the radioactivity were recovered, respectively, in the urine within 48 h. HPLC-UV and LC/MS analyses demonstrated that the major urinary metabolite was the glucuronide of M-2 (desmethyl metabolite at the o-methoxyphenoxy group) followed by M-5, the M-3 glucuronide, and the M-4 glucuronide, in that order. In the bile sample, amosulalol carbamoyl glucuronide was found as a new metabolite of this drug.

• 公益社団法人日本薬学会の論文
• 2007-08-01

著者

• SUZUKI Katsuhiro

  Drug Metabolism Laboratories, Drug Development Division, Yamanouchi Pharmaceutical Co., Ltd.

• Kamimura Hidetaka

  Drug Metabolism Department Product Development Laboratories Yamanouchi Pharmaceutical Co. Ltd.

• Suzuki Katsuhiro

  Drug Metabolism Research Laboratories Drug Discovery Research Astellas Pharma Inc.

関連論文

• ヒト薬物動態関連遺伝子の発現に対するHNF4αの寄与をsiRNA発現アデノウイルスを用いて解析する
• Application of LC-NMR for Characterization of Rat Urinary Metabolites of Zonampanel Monohydrate (YM872)
• Assessment of Chimeric Mice with Humanized Liver as a Tool for Predicting Circulating Human Metabolites
• Highly sensitive method for the determination of tamsulosin hydrochloride in human plasma dialysate, plasma and urine by high-performance liquid chromatography-electrospray tandem mass spectrometry
• Pharmacokinetics and Metabolism of an α,β-Blocker, Amosulalol Hydrochloride, in Mice : Biliary Excretion of Carbamoyl Glucuronide(Biopharmacy)
• α-GLUCOSIDE FORMATION in vitro
• Determination of solifenacin succinate, a novel muscarinic receptor antagonist, and its major metabolite in rat plasma by semi-micro high performance liquid chromatography
• Identification of Enzymes Responsible for the N-Oxidation of Darexaban Glucuronide, the Pharmacologically Active Metabolite of Darexaban, and the Glucuronidation of Darexaban N-Oxides in Human Liver Microsomes

スポンサーリンク