Pharmacology, pharmacokinetics and clinical development of haloperidol decanoate.

The absorption mechanism of haloperidol decanoate from the intramuscular depot was studied in dogs. Haloperidol, a pharmacologically active molecule characterised by selective dopamine antagonism, was detectable in plasma within one hour after dosing. Peak plasma levels were obtained within three to seven days. After single and repeated doses of haloperidol decanoate, plasma levels were found to be dose related. Human pharmacokinetics in schizophrenic patients were studied by giving four-weekly deep intramuscular injections of haloperidol decanoate at doses equivalent to the patients' previous antipsychotic medication. Within each interval between doses, haloperidol plasma levels were maximal within the first week after each dose, decaying with an average half-life of three weeks. Steady-state was reached within three months giving therapeutic plasma levels in the same range as those found during oral treatment with haloperidol. Open and double-blind clinical trials have demonstrated the clinical efficacy of haloperidol decanoate given four-weekly by deep intramuscular injection over a dose range from 50 to 300 mg, principally in schizophrenic patients. Low incidences of extrapyramidal side effects were noted, often allowing a reduction of antiparkinsonian medication required through previous antipsychotic treatment.