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Absorption, excretion and metabolism of oral bromperidol in rats and dogs

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Summary

After an oral dose of 0.16 mg/kg, the absorption, excretion and metabolism of bromperidol-3H, an analogue of the neuroleptic haloperidol, were studied in dogs. In rats, the tissue distribution, excretion and metabolism were followed.

Plasma levels of unchanged bromperidol in the dog were maximal 4–7 hours after dosing and corresponded to 4 ng/ml. Afterwards, elimination of intact drug was biphasic with a terminal half-life of approximately 30 hours. Levels of radioactivity decreased more slowly, probably due to the presence of tritiated water in the plasma.

The radioactivity in the urine of both rats (35% of the dose) and dogs (46% of the dose within 4 days), consisted mainly of polar acidic metabolites. Inverse isotope dilution demonstrated that the polar urinary fraction was due to the glycine conjugate ofp-fluorophenylacetic acid almost completely in the rat but only partly in the dog. Unchanged bromperidol was present in trace amounts in the urine, and only 10% of the dose was excreted with the faeces for both rats and dogs. Oxidative JV-dealkylation was the major metabolic pathway in both species and the fate of bromperidol was similar to that of haloperidol.

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Authors and Affiliations

  1. Department of Drug Metabolism, Janssen Pharmaceutica, B-2340, Beerse, Belgium

    J. Heykants, W. Meuldermans & M. Michiels

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  1. J. Heykants
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  2. W. Meuldermans
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  3. M. Michiels
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Heykants, J., Meuldermans, W. & Michiels, M. Absorption, excretion and metabolism of oral bromperidol in rats and dogs. European Journal of Drug Metabolism and Pharmacokinetics 3, 111–117 (1978). https://doi.org/10.1007/BF03189379

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  • DOI: https://doi.org/10.1007/BF03189379

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