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Isolation and characterization of the urinary metabolites of arbaprostil in the male dog after intravenous administration

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Summary

The profile of urinary metabolites of3H-arbaprostil was characterized in the male dog after intravenous administration. The major metabolites were purified and their structures deduced by gas chromatography/mass spectrometry (GC/MS) studies after conversion to the methyl ester-methoxime-trimethylsilyl ether derivatives, aided by GC with simultaneous radioactivity monitoring. The identified metabolites accounted for 96% of the urinary excretion products. β-Oxidation of the carboxy side-chain of arbaprostil to 15-methyl-2,3,4,5-tetranor PGE1, via the 15-methyl-2,3-dinor PGE: intermediate, appeared to be the most significant metabolic pathway. In contrast to the rat. the following were observed in the dog: glucuronic acid conjugation of the 15-methyl-2,3,4,5-tetranor PGE, and PGA metabolites; detection of the l5-methyl-2,3-dinor PGE2 intermediate; absence of 19-hydroxyl-15-methyl-2,3.4,5.-tetranor PGA. and PGB metabolites; oxidation at C-20; and excretion of some parent drug.

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Authors and Affiliations

  1. Drug Metabolism Research, The Upjohn Company, 49001, Kalamazoo, Michigan, USA

    Bruce A. Thornburgh, S. Robert Shaw, George E. Bronson & Asoka J. Wickrema Sinha

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  1. Bruce A. Thornburgh
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  2. S. Robert Shaw
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  3. George E. Bronson
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  4. Asoka J. Wickrema Sinha
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Thornburgh, B.A., Shaw, S.R., Bronson, G.E. et al. Isolation and characterization of the urinary metabolites of arbaprostil in the male dog after intravenous administration. European Journal of Drug Metabolism and Pharmacokinetics 13, 113–121 (1988). https://doi.org/10.1007/BF03191312

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  • DOI: https://doi.org/10.1007/BF03191312

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