Mallikaarjun Suresh, Salazar Daniel E, Bramer Steven L
Otsuka Maryland Research Institute, 2440 Research Boulevard, Rockville, MD 20850, USA.
J Clin Pharmacol. 2004 Feb;44(2):179-87. doi: 10.1177/0091270003261901.
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.
两项为期14天、安慰剂对照、双盲研究评估了新型抗精神病药物阿立哌唑在健康男性受试者中的空腹药代动力学、安全性和耐受性。在研究1中，37名受试者被随机分为每日一次服用阿立哌唑5毫克、10毫克、15毫克、20毫克或安慰剂组。在研究2中，11名受试者被随机分为阿立哌唑组（剂量从10毫克/天滴定至30毫克/天）或安慰剂组。阿立哌唑在5至30毫克/天范围内具有线性药代动力学，由二室开放模型描述，具有一级吸收。在研究1中，阿立哌唑的平均消除半衰期为47至68小时，表观全身清除率（CL/F）约为3.45升/小时。在研究2中，平均消除半衰期为59小时（CL/F约为4.0升/小时）。不良事件一般为轻至中度，本质上是短暂的，通常在给药的前3天内出现。临床实验室评估、心电图、脑电图和催乳素水平在研究期间均未显示出临床显著变化。
