Summary
[14C] Haloperidol decanoate was hydrolysed by partially purified carboxylesterase but not in plasma, blood, lymph and lymphatic liquid. These fluids inhibited the enzyme-mediated hydrolysis of the ester. Within the same incubation period as above, the ester was found hydrolysed to various extents in cell cultures of isolated rat liver cells, of human and rat lymphocytes and of established cell lines (BGM cells, WI-38 cells and L6 cells). Thus, the hydrolysis of the ester was demonstratedin vitro with use of viable cell cultures instead of enzyme preparation. From the time course study on the metabolism of haloperidol decanoate in cell cultures, it was concluded that haloperidol decanoate was first concentrated in the cells and hydrolysed to haloperidol. Based on these results, the metabolic sequencesin vivo leading to the formation of active principle haloperidol after intramuscular administration of its decanoate were discussed.
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This work was done in the periods of August, 1984 – December, 1985.
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Oh-E, Y., Miyazaki, H., Matsunaga, Y. et al. Hydrolysis of haloperidol decanoatein vitro by cultured cells. European Journal of Drug Metabolism and Pharmacokinetics 12, 183–188 (1987). https://doi.org/10.1007/BF03189895
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DOI: https://doi.org/10.1007/BF03189895