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Research ArticleArticle

In Vivo Metabolism and Mass Balance of 4-[4-Fluorophenoxy]benzaldehyde Semicarbazone in Rats

Kumar Ramu, Gilbert N. Lam and Helen Hughes
Drug Metabolism and Disposition October 2000, 28 (10) 1153-1161;
Kumar Ramu
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Gilbert N. Lam
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Helen Hughes
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Abstract

The pharmacokinetics, mass balance, tissue distribution, and metabolism of Co 102862 was investigated in rats after a single oral dose. [14C]Co 102862 showed multiexponential pharmacokinetics in rat plasma with an extensive distribution phase. After p.o. administration (∼10 mg/kg), the half-lives were long for total radioactivity compared with unchanged Co 102862. Profiles of rat urine and bile suggest that Co 102862 is extensively metabolized in vivo. [14C]Co 102862 was extensively distributed into all tissues, with the fatty tissues and secretory glands tissues containing the highest radioactivity. Elimination of radioactivity from the tissues had an estimated half-life of 14 days. A total of 91% of the administered radioactivity was recovered in both intact and bile-duct cannulated rats over 120 and 48 h, respectively, with the majority (∼74%) of the radioactivity being excreted in the urine. Approximately 10% of the total radioactivity remained in the tissues on day 5 and decreased with time to ∼3% on day 28. Bile-duct cannulated experiments show the enterohepatic circulation is an important route of elimination and reabsorption. Six metabolites were identified in the urine and bile of which the carboxylic acid was the major metabolite. The carboxylic acid was the only metabolite found in plasma and was probably responsible for the radioactivity in the tissues.

Footnotes

  • Send reprint requests to: Kumar Ramu, Quest Pharmaceutical Services, Delaware Technology Park, 3 Innovation Way, Suite 240, Newark, DE 19711. E-mail: Kumar.Ramu{at}questpharm.com

  • Abbreviations used are::
    Co 102862
    4-[4-fluorophenoxy]benzaldehyde semicarbazone
    Co 200653
    4-(4-fluorophenoxy)benzoic acid
    Co 103084
    4-(4-fluorophenyl)benzoylsemicarbazide
    MS
    mass spectrometry
    MS/MS
    tandem MS
    LC-MS
    liquid chromatography-MS
    LC-MS/MS
    liquid chromatography-tandem MS
    rt
    retention time
    • Received February 16, 2000.
    • Accepted July 20, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 28 (10)
Drug Metabolism and Disposition
Vol. 28, Issue 10
1 Oct 2000
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Research ArticleArticle

In Vivo Metabolism and Mass Balance of 4-[4-Fluorophenoxy]benzaldehyde Semicarbazone in Rats

Kumar Ramu, Gilbert N. Lam and Helen Hughes
Drug Metabolism and Disposition October 1, 2000, 28 (10) 1153-1161;

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Research ArticleArticle

In Vivo Metabolism and Mass Balance of 4-[4-Fluorophenoxy]benzaldehyde Semicarbazone in Rats

Kumar Ramu, Gilbert N. Lam and Helen Hughes
Drug Metabolism and Disposition October 1, 2000, 28 (10) 1153-1161;
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