[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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Deberdt R., Elens P., Berghmans W., Heykants J., Woestenborghs R., Driesens F., Reyntjens A. and van Wijngaarden I. (1980): Intramuscular haloperidol decanoate for neuroleptic maintenance therapy. Efficacy, dosage schedule and plasma levels. An open multicenter study. Acta Psychiat Scand.,62, 356–363.
Ayd F.J. (1980): Haloperidol decanoate: The latest depot neuroleptic. Int. Drug Ther. Newsl.,15, 5–7.
Nambu K., Miyazaki H., Nakanishi Y., Oh-e Y., Matsunaga Y. and Hashimoto M. (1987): Enzymatic hydrolysis of haloperidol decanoate and its inhibition by proteins. Biochem. Pharmacol.,36, 1715–1722.
Matsunaga Y., Oh-e Y., Nambu K., Kagemoto A., Negoro T., Sekine Y. and Miyazaki H. (1985): Distribution of intramuscularly administered [14C] haloperidol decanoate in rats. Jpn. Pharmacol. Ther. (in Japanese),13, 6617–6628.
Negoro T., Nakao M., Kagemoto A. and Hashimoto M. (1982): Synthesis of [carboxyl-14C]etofenamate and its major metabolite. Radioisotopes (in Japanese),31, 636–640.
Bollman J.L., Cain J.C. and Grindlay J.H. (1948): Techniques for the collection of lymph from the liver small intestine, or thoracic duct of the rat. J. Lab. Clin. Med.,33, 1349–1352.
O’Hara N. and Brodde O.E. (1984): Identical binding properties of (±)- and (−)-125 iodocyanopindolol to β-adrenoceptors in intact human lymphocytes. Arch. Int. Pharmacodyn.,272, 24–39.
Matsunaga Y., Nambu K., Oh-e Y., Miyazaki H. and Hashimoto M. (1987): Absorption of intramuscularly administered [14C] haloperidol decanoate in rats. Eur. J. Drug Metab. Pharmacokin., (this issue).
Matsumoto K., Morino N., Fujii T., Furukawa H., Nambu K., Matsunaga Y., Miyazaki H. and Hashimoto M. (1982): Disposition and metabolism of [14C]etofenamate in rats (I). Pharmacokinetics of [14C]etofenamate and [14C]flufenamic acid after intravenous, oral and subcutaneous administration. Jpn. Pharmacol. Ther. (in Japanese),10, 4401–4407.
Matsunaga Y., Nambu K., Oh-e Y., Miyazaki H. and Hashimoto M. (1986): Excretion and metabolism of intramuscularly administered [14C]haloperidol decanoate in rats. Arzneim. Forsch.,36, 453–456.
Miyazaki H., Matsunaga Y., Nambu K., Oh-e Y. and Hashimoto M. (1986): Disposition and metabolism of [14C]haloperidol in rats. Arzneim. Forsch.,36, 443–452.
Yale H.L. (1978): The long-acting neuroleptics: A retrospective appraisal. Drug Metab. Rev.,8, 251–262.
Jann M.W., Ereshefsky L. and Saklad S.R. (1985): Clinical pharmacokinetics of the depot antipsychotics. Clin. Pharmacokin.,10, 315–333.
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
- Haloperidol decanoate
- cultured cells