Metabolic Pathways and Pharmacokinetics of BOF-4272,a Sulfoxide-Containing Drug, in the Dog : In Vivo and in Vitro Studies

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概要

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• BOF-4272,(±)-8-(3-methoxy-4-phenylsulfinylphenyl)pyrazolo[1,5-a]-1,3,5-triazine-4(1H)-one, is a new drug intended for the treatment of hyperuricemia. This report describes the detailed metabolic pathways of BOF-4272 in the dog. The metabolic pathways were investigated using the metabolites found in plasma, urine, and feces after intravenous or oral administration of BOF-4272,as well as the metabolites found in the liver S9 incubation mixture after the addition of BOF-4272 or BOF-4269. BOF-4269 (the sulfide metabolite of BOF-4272) was the only metabolite detected in plasma and feces after the intravenous or oral administration of BOF-4272. BOF-4269 was detected in dog plasma after a lag time following the oral administration of BOF-4272,and the C_<max> and AUC_<0-t> of BOF-4269 were higher in fed dogs than in fasted dogs after the oral administration of BOF-4272. A small amount of BOF-4269 was detected in dog plasma immediately after the intravenous administration of BOF-4272. Only BOF-4276 (the sulfone metabolite of BOF-4272) was detected in the S9 incubation mixture after the addition of BOF-4272. Mainly BOF-4272 was detected and small amounts of BOF-4276 and M-1 (the hydroxy metabolite of BOF-4269) were detected in the S9 incubation mixture after the addition of BOF-4269. These findings suggest that BOF-4272 is mainly metabolized to BOF-4269 by the intestinal flora in dogs, whereas little of this drug is metabolized to BOF-4269 in the dog liver. In conclusion, this work has allowed us to formulate the proposed metabolic pathways of BOF-4272 in the dog.

• 公益社団法人日本薬学会の論文
• 1999-12-15

著者

• NAITO Shinsaku

  Research and Development Center, Otsuka Pharmaceutical Factory, Inc.

• Nishimura M

  Research And Development Center Otsuka Pharmaceutical Factory Inc.

• Nishimura Masuhiro

  Department Of Drug Metabolism Division Of Pharmacology Drug Safety And Metabolism Otsuka Pharmaceuti

• Naito S

  Otsuka Pharmaceutical Factory Inc. Tokushima Jpn

• Naito Shinsaku

  Naruto Research Institute Laboratory Of Drug Metabolism Research Otsuka Pharmaceutical Factory Inc.

• Nogawa Hiroyuki

  Naruto Research Institute Otsuka Pharmaceutical Factory Inc.

• NISHIMURA Masuhiro

  Naruto Research Institute, Otsuka Pharmaceutical Factory, Inc.,

• YOSHITSUGU Hiroki

  Nutrition Research Institute Otsuka Pharmaceutical Factory, Inc.,

• Yoshitsugu Hiroki

  Division Of Pharmacology Drug Safety And Metabolism Otsuka Pharmaceutical Factory Inc.

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