Pharmacokinetics, tolerability, and safety of aripiprazole following multiple oral dosing in normal healthy volunteers.
Two 14-day, placebo-controlled, double-blind studies evaluated the fasting pharmacokinetics, safety, and tolerability of aripiprazole, a new antipsychotic, in healthy male subjects. In Study 1, 37 subjects were randomized to aripiprazole 5 mg, 10 mg, 15 mg, 20 mg, or placebo once daily. In Study 2, 11 subjects were randomized to aripiprazole, titrated from 10 to 30 mg/day, or placebo. Aripiprazole had linear pharmacokinetics over 5 to 30 mg/day, which were described by a two-compartment open model, with first-order absorption. In Study 1, mean elimination half-life ranged from 47 to 68 hours with aripiprazole, with apparent systemic clearance (CL/F) of approximately 3.45 L/h. In Study 2, mean elimination half-life was 59 hours (CL/F approximately 4.0 L/h). Adverse events were generally mild to moderate, were transient in nature, and commonly occurred within the first 3 days of dosing. Clinical laboratory assessments, electrocardiogram, electroencephalogram, and prolactin levels showed no clinically significant changes during the studies.
Mallikaarjun
Suresh
S
Otsuka Maryland Research Institute, 2440 Research Boulevard, Rockville, MD 20850, USA.
Salazar
Daniel E
DE
Bramer
Steven L
SL
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D019540:Area Under Curve; D000068180:Aripiprazole; D005215:Fasting; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole