Pharmacokinetics of RP5063 Following Single Doses to Normal Healthy Volunteers and Multiple Doses Over 10 Days to Stable Schizophrenic Patients

RP5063, a multimodal dopamine (D)–serotonin (5‐HT) stabilizer, possesses high affinity for D(2/3/4) and 5‐HT(1A/2A/2B/2C/6/7) receptors and moderate affinity for the serotonin transporter. Two phase I studies characterized the pharmacokinetics of a single dose (10 and 15 mg fasting, 15 mg fed/fasting) in healthy volunteers and multiple doses (10, 20, 50, and 100 mg fed) over 10 days in patients with stable schizophrenia. RP5063 displayed a dose‐dependent C(max) at 4 to 6 h, linear dose proportionality for both C(max) and AUC, and a half‐life between 40 and 71 h. In the single‐dose study, food slightly increased the extent of drug absorption. In the multiple‐dose study, steady‐state was approached after 120 h of daily dosing. Pooled data in the single‐dose study indicate that the pharmacokinetic profile appears to be comparable between Japanese and Caucasians. RP5063 appears to have a straightforward pharmacokinetic profile that supports for phase II and III evaluation as a once‐daily oral administered agent.