Formation Route of Sulfur-Containing Metabolites of Afloqualone, a New Centrally Acting Muscle Relaxant, in Rat

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概要

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• The formation route of the sulfur-containing metabolites of afloqualone [6-amino-2-fluoromethyl-3-(o-tolyl)-4(3H)-quinazolinone, AFQ], a centrally acting muscle relaxant, was studied in rats. When ^<14>C-N-acetyl AFQ 2-mercapturate (AFQM) methyl ester was administered orally to normal rats, it was excreted in the bile as AFQM, one of the major biliary metabolites of AFQ, and in the urine as sulfur-containing metabolites of AFQ such as methylsulfinyl and methylsulfonyl metabolites of AFQ. This indicated that AFQM was a precursor of these methylsulfinyl and -sulfonyl metabolites. Pretreatment of rats with antibiotics significantly reduced the urinary excretion of ^<14>C-AFQM and its metabolites as compared with normal rats. Oral administration of ^<14>C-AFQ to antibiotics-treated rats also significantly reduced the amounts of the sulfur-containing metabolites excreted into the urine, but did not affect the amounts of other non-sulfur-containing metabolites. In addition, oral administration of ^<14>C-AFQ to bile-duct-ligated rats gave results similar to those in the antibiotics-treated rats. These results indicate that in normal rats microfloral metabolism is necessary for the formation of the methylsulfinyl and -sulfonyl metabolites from AFQM and other unidentified mercapturate pathway conjugates excreted into the bile. The metabolites of AFQ produced by the microflora are reabsorbed into the systemic circulation, processed by further metabolism in the liver, and in turn excreted in the urine.

• 公益社団法人日本薬学会の論文
• 1983-08-25

著者

• 大塚 峯三

  Pharmacological Research Laboratory Tanabe Seiyaku Co. Ltd.

• 針谷 祥一

  Pharmacological Research Laboratory Tanabe Seiyaku Co., Ltd.

• 古内 論

  田辺製薬株式会社生物研究所

• 古内 論

  Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd.

• 針谷 祥一

  Biological Research Laboratory Tanabe Seiyaku Co. Ltd.

• 大塚 峯三

  田辺製薬

関連論文

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• Metabolism of Afloqualone, a New Centrally Acting Muscle Relaxant, in the Rat
• Synthesis of the Metabolites of Afloqualone and Related Compounds
• 消化管運動調律薬 Trimebutine Maleate のラット及びマウスにおける代謝尿、胆汁及び血漿中代謝物の定性及び測定
• Formation Route of Sulfur-Containing Metabolites of Afloqualone, a New Centrally Acting Muscle Relaxant, in Rat
• New Approach to the Hepatic First-Pass Effect by Whole-Body Autoradiography
• THE β-GLUCOSIDATION AND β-GLUCURONIDATION OF PANTOTHENIC ACID COMPARED WITH P-NITROPHENOL IN DOG LIVER MICROSOME

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