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Metabolism of sulpiride: Determination of the chemical structure of its metabolites in rat, dog and man

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Summary

Results concerning the metabolism and pharmacokinetics of Sulpiride in rats have been previously reported.

The present study describes the separation, quantification and determination of the chemical structure of the sulpiride metabolites found in the urine and plasma of rats, dogs and humans. The metabolites were separated by means of multicolumn HPLC and their structure then determined by mass spectrometry, IR and UV spectroscopy. Furthermore, the chemical structure of the six isolated metabolites as well as unchanged product obtained by biological pathways was confirmed by comparison with that of the synthesized reference products.

The metabolites obtained from rat and dog were: 5-aminosulfonyl-N-[(1-ethyl-2-pyrrohdinyl)methyl]-2-hydroxybenzamide (in rat only), 5-amtaosulfonyl-N-[(2-pyrroBdlnyl)methyl]-2-hydroxybenzamide,5-anunosulfonyl-N-[(l-ethyl-5-oxo-2-pyrroUdin zamide, 5-aminosulfonyl-2-methoxybenzamide, 5-aminosulfonyl-N-[(l-ethyl-5-oxo-2-pyrrolidinyl)methyl)-2-methoxybenzamide,5-aminosulfonyl-N-[(2-pyrrolidinyl)methyl]-2-methoxybenzamide.

In the rat, metabolites represented 56% of the administered drug of which 38% were conjugates; in the dog, they represented 15% of which 4% were conjugates. None of these metabolites was found in human urine; the pharmacological properties of sulpiride could therefore be attributed to the unchanged product.

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Authors and Affiliations

  1. Laboratory of Drug Metabolism, Department of Pharmacology, University of Geneva, Geneva

    F. R. Sugnaux & A. Benakis

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  1. F. R. Sugnaux
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  2. A. Benakis
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A first account of this work was presented at the Seventh International Congress of Pharmacology, IUPHAR, Paris, France, July 16–21,1978.

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Sugnaux, F.R., Benakis, A. Metabolism of sulpiride: Determination of the chemical structure of its metabolites in rat, dog and man. European Journal of Drug Metabolism and Pharmacokinetics 3, 235–248 (1978). https://doi.org/10.1007/BF03189389

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  • DOI: https://doi.org/10.1007/BF03189389

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