The Pharmacokinetics of Long-Acting Antipsychotic Medications
Stefano Spanarello and Teresa La Ferla
Affiliation: NHS, Health Trust No. 3 Umbria, Mental Health Department, Day Hospital, Via Arcamone s.n.c. 06034 Foligno, Perugia, Italia.
Keywords: Absorption, antipsychotics, kinetics, long-acting, plasma level, relapse.
The depot antipsychotics are synthesized by esterification of the active drug to a long chain fatty acid and the
resultant compound is then dissolved in a vegetable oil, with the exception of some molecules of new generation
characterized by microcrystalline technologies. The absorption rate constant is slower than the elimination rate constant
and therefore, the depot antipsychotics exhibit 'flip-flop' kinetics where the time to steady-state is a function of the
absorption rate, and the concentration at steady-state is a function of the elimination rate The pharmacokinetics of depot
antipsychotic medications are such that an intramuscular injection given at intervals from 1 to 4 weeks will produce
adequate plasma concentrations that are sufficient to prevent relapse over the dosage interval. Such medication is useful in
patients who do not reliably take their oral medication. The pharmacokinetics and clinical actions of various depot
formulations of antipsychotic drugs have been extensively studied. The clinical pharmacokinetics of the depot
antipsychotics for which plasma level studies are available (i.e. fluphenazine enanthate and decanoate, haloperidol
decanoate, bromperidol decanoate, clopenthixol decanoate, flupenthixol decanoate, perphenazine onanthat, pipotiazine
undecylenate, pipotiazine palmitate, fluspirilene, Long-acting injectable risperidone, olanzapine pamoate, paliperidone
palmitate, Long-acting iloperidone, Long-acting injectable aripiprazole) are reviewed. The proper study of these agents
has been handicapped until recently by the necessity of accurately measuring subnanomolar concentrations in plasma.
Their kinetic properties, the relationship of plasma concentrations to clinical effects, and conversion from oral to
injectable therapy are discussed.
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