Pharmacokinetics and Pharmacodynamics of Lurasidone Hydrochloride, a Second-Generation Antipsychotic: A Systematic Review of the Published Literature

Lurasidone hydrochloride, a benzisothiazol derivative, is a second-generation (atypical) antipsychotic agent that has received regulatory approval for the treatment of schizophrenia in the US, Canada, the EU, Switzerland, and Australia, and also for bipolar depression in the US and Canada. In addition to its principal antagonist activity at dopamine D₂ and serotonin 5-HT_2A receptors, lurasidone has distinctive 5-HT₇ antagonistic activity, and displays partial agonism at 5-HT_1A receptors, as well as modest antagonism at noradrenergic α_2A and α_2C receptors. Lurasidone is devoid of antihistaminic and anticholinergic activities. It is administered once daily within the range of 40–160 mg/day for schizophrenia and 20–120 mg/day for bipolar depression, and its pharmacokinetic profile requires administration with food. In adult healthy subjects and patients, a 40 mg dose results in peak plasma concentrations in 1–3 h, a mean elimination half-life of 18 h (mostly eliminated in the feces), and apparent volume of distribution of 6173 L; it is approximately 99 % bound to serum plasma proteins. Lurasidone’s pharmacokinetics are approximately dose proportional in healthy adults and clinical populations within the approved dosing range, and this was also found in a clinical study of children and adolescents. Lurasidone is principally metabolized by cytochrome P450 (CYP) 3A4 with minor metabolites and should not be coadministered with strong CYP3A4 inducers or inhibitors. Lurasidone does not significantly inhibit or induce CYP450 hepatic enzymes.