Lurasidone – pharmacodynamic and pharmacokinetic properties, clinical potential and interaction risk

Abstract

Lurasidone is a novel second-generation antipsychotic approved for the treatment of schizophrenia and bipolar depression in adults. It displays high affinity for D2 and 5-HT2A and 5-HT7 receptors, moderate affinity for 5-HT1A and α2C-noradrenergic receptors, and negligible affinity for histamine H1 and muscarinic M1 receptors. It acts as potent D2, 5-HT2A and 5-HT7 antagonist and partial 5-HT1A agonist. Lurasidone taken orally is rapidly absorbed with the time to maximum concentration of 1-3 hours. Lurasidone should be taken with food (at least 350 kcal) due to limited absorption. The mean elimination half-life of lurasidone is 18.1–25.5 hours for doses 20–80 mg/day and 28.8–37.4 hours for doses of 120–160 mg/day. Steady-state is reached within 7 days. The drug is metabolised via CYP 3A4 and excreted mainly in faeces (67–80%) and with urine (about 8–19%). The use of lurasidone with strong inhibitors or inducers of CYP 3A4 (e.g. ketoconazole, erythromycin, or carbamazepine, respectively) is contraindicated. In the case of combined treatment of lurasidone and moderate inhibitors of CYP 3A4, the dose of lurasidone should be decreased to 40 mg/day. Lurasidone is an inhibitor of P-glycoprotein and could increase the level of digoxin and potentate the side effects risk of this drug. Pomelo, grapefruit, or a large amount of oranges should be avoided in the diet during treatment with lurasidone. Pharmacodynamic properties of lurasidone underlie its antipsychotic, antidepressant, precognitive, and sleep-awake rhythm normalising activity.