Pharmacokinetics

Like antidepressants, antipsychotics are well absorbed and distributed after oral administration. In situations where very rapid relief of symptoms or disturbed behaviour is required, faster uptake into plasma can be achieved through the intramuscular route. Again in common with antidepressants, antipsychotics are mainly metabolised by cytochrome P450 isoenzymes in the liver, e.g. CYP 2D6 (zuclopenthixol, risperidone [Table 19.2a]), CYP 3A4 (sertindole [Table 19.2b]), CYP 1A2 (olanzapine, clozapine). Metabolism of some compounds is particularly complex (e.g. chlorpromazine, haloperidol), involving more than one main pathway, utilising several P450 enzymes or resulting in the production of many inactive metabolites. Antipsychotic plasma levels can be increased or decreased by co-prescription of drugs which are inhibitors, inducers or substrates of the same isozyme. Amisulpride is an exception to the general rule as it is eliminated by the kidneys without hepatic metabolism.

Examples of plasma half-lives for antipsychotics include quetiapine 7 h, clozapine 12 h, haloperidol 18 h and olazapine 33 h. Depot intramuscular injections are available from which drug is released over 2-4 weeks.

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