SAFETY, TOLERABILITY, AND EFFECT OF FOOD ON THE PHARMACOKINETICS OF ILOPERIDONE (HP-873), A POTENTIAL ATYPICAL ANTIPSYCHOTIC

Iloperidone (HP 873) is a D-2 and 5-HT2 receptor-antagonist that is un der development as a potential atypical antipsychotic agent. Two studi es on iloperidone evaluated its safety and tolerability, made a prelim inary pharmacokinetic assessment of single 3- and 5-mg doses, and dete rmined the effect of food on its tolerability and pharmacokinetics in healthy volunteers after single 3-mg doses. Iloperidone was well absor bed orally in fasted subjects. The C-max occurred approximately 2 to 3 hours after administration of a single 3- or 5-mg dose. The pharmacok inetic parameters increased with the dose between 3 and 5 mg (from 2.2 to 5.2 ng/mL for C-max, and 16 to 50 ng/ml . h for AUC). Iloperidone was eliminated slowly, with a mean t(1/2) of 13.5 to 14.0 hours. Coadm inistration with food did not significantly affect AUC, t(max), or C-m ax. These results indicate that the rate of iloperidone's absorption i s decreased, but the overall bioavailability is unchanged, when the dr ug is taken with food. Orthostatic hypotension, dizziness, and somnole nce were the most commonly reported adverse events. Coadministration o f food reduced the incidence and severity of these events.