Summary
The excretion and metabolism of tritium-labelled loperamide was studied in male Wistar rats after an oral dose of 1.25 mg/kg. The results were compared with the data previously obtained, using loperamide-3H with the tritium-label in the metabolically unstable methyl groups of the tertiary amide. Loperamide and its metabolites were excreted mainly with the faeces. About 9% of the dose was excreted with the urine, predominantly as metabolites. Total excretion of radioactivity amounted to 93% of the dose within 4 days. Residual radioactivity in the tissues was negligible 4 days after treatment, indicating that loperamide and its metabolites did not accumulate in the tissues of the rat. Biliary excretion amounted to 56% of the dose up to 48 hours and consisted mainly of glucuronides of basic metabolites. The major metabolites in the urine were bis-desmethylated loperamide (R 21 345) and 4-(4-chlorophenyl)-4-hydroxy-piperidine (R 1515). In the bile were present mono- and bis-desmethylated loperamide, whereas in the faeces a large part of the radioactivity was due to unchanged loperamide (about 30% of the dose). Oxidative ./V-dealkylation, including demethylation, seemed to be the major metabolic pathway.
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Heykants, J.J.P., Meuldermans, W.E.G., Knaeps, A.G. et al. The excretion and netabolism of the antidiarrhoeal loperamide in the Wistar rat. European Journal of Drug Metabolism and Pharmacokinetics 2, 81–91 (1977). https://doi.org/10.1007/BF03189288
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DOI: https://doi.org/10.1007/BF03189288