Chen Xia, Wang Hongyun, Jiang Ji, Chen Rui, Zhou Ying, Zhong Wen, Liu Hongzhong, Hu Pei
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 41 Damucang Alley, Xicheng District, Beijing, 100032, China.
Clin Drug Investig. 2014 Mar;34(3):213-22. doi: 10.1007/s40261-013-0167-9.
Blonanserin is a novel atypical antipsychotic drug acting as a mixed serotonin 5-HT2A and dopamine D2 receptor antagonist. This study investigated the pharmacokinetics and safety of blonanserin in healthy Chinese males.
This was an open-label trial with two parts. Twenty-four subjects were enrolled in part A to receive a single fasting dose of 4 or 8 mg blonanserin (each n = 12); part B recruited 12 subjects and administered single and sequentially twice-daily multiple postprandial doses of blonanserin 2 mg for 9 days. Serial blood samples were taken for the bioassay of plasma blonanserin and its four metabolites during both sub-studies. Safety was assessed, including repeat measurements of fasting serum prolactin, insulin, triglyceride and cholesterol.
Blonanserin was rapidly absorbed, accompanied with immediate plasma concentration elevation of the N-oxide form (M2) and gradual rises of the N-deethylated form (M1) and its downstream metabolites. The mean elimination half-life of blonanserin (7.7-11.9 h) was much longer than that of M2 (1.2-1.3 h) but shorter than that of M1 (26.4-31.4 h) after single fasting doses. After food intake, a single dose of 2 mg blonanserin resulted in total exposure and peak concentrations of blonanserin similar to those observed with a single fasting dose of blonanserin 4 mg. Moreover, the relationship of metabolite over parent compound ratio was different between M1 and M2 after single and multiple postprandial administrations (single dose vs multiple dose: M1, 0.33 vs 0.75; M2, 0.13 vs 0.067). Mild but transient increases of prolactin, insulin and triglyceride were observed.
The pharmacokinetics of blonanserin in Chinese subjects were similar to those observed in Japanese subjects. This study suggested that food intake not only increases the bioavailability of blonanserin but differently affects the pharmacokinetics of its metabolites as well. The drug was safe and well tolerated in healthy Chinese males.
布南色林是一种新型非典型抗精神病药物，作为5-羟色胺5-HT2A和多巴胺D2受体的混合拮抗剂。本研究调查了布南色林在中国健康男性中的药代动力学及安全性。
这是一项分为两部分的开放标签试验。A部分纳入24名受试者，接受4毫克或8毫克布南色林的单次空腹给药（各12名）；B部分招募12名受试者，给予布南色林2毫克的单次及连续每日两次餐后多次给药，持续9天。在两个子研究期间，采集系列血样用于血浆布南色林及其四种代谢物的生物测定。评估安全性，包括空腹血清催乳素、胰岛素、甘油三酯和胆固醇的重复测量。
布南色林吸收迅速，伴随N-氧化物形式（M2）的血浆浓度立即升高，以及N-去乙基化形式（M1）及其下游代谢物的逐渐升高。单次空腹给药后，布南色林的平均消除半衰期（7.7 - 11.9小时）远长于M2（1.2 - 1.3小时），但短于M1（26.4 - 31.4小时）。进食后，单次2毫克布南色林给药导致的布南色林总暴露量和峰值浓度与单次空腹4毫克布南色林给药时观察到的相似。此外，单次和多次餐后给药后，M1和M2的代谢物与母体化合物比率关系不同（单剂量与多剂量：M1，0.33对0.75；M2，0.13对0.067）。观察到催乳素、胰岛素和甘油三酯有轻微但短暂升高。
布南色林在中国受试者中的药代动力学与在日本受试者中观察到的相似。本研究表明，进食不仅增加布南色林的生物利用度，还对其代谢物的药代动力学有不同影响。该药物在健康中国男性中安全且耐受性良好。
