Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Clin Ther. 2012 Jun;34(6):1432-9. doi: 10.1016/j.clinthera.2012.04.027. Epub 2012 May 16.
Risperidone (RIS), an atypical antipsychotic drug, is used for the treatment of psychoses associated with schizophrenia and other psychiatric disorders in adult and pediatric populations. An oral dispersible tablet formulation of risperidone has been developed. This study was conducted to provide support for marketing authorization of this drug in China.
This study was designed to compare the pharmacokinetic (PK) properties and bioavailability of 2 RIS formulations-the dispersible formulation (test) and a branded formulation (reference) in healthy male Chinese volunteers.
This single-dose, randomized-sequence, open-label, 2-period crossover study involved 22 healthy male Chinese volunteers. Equal numbers of eligible participants were randomly assigned to receive either the test drug (2 mg) or the same dose of the reference formulation, followed by a 2-week washout period and administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Blood samples were collected before dosing and at 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72, and 96 hours after dosing. Plasma concentrations of RIS and its active metabolite, 9-hydroxyrisperidone (9-OH-RIS), were measured using LC-MS/MS. The safety profile was evaluated by recording adverse events (AEs), assessed using physical examination including vital signs, spontaneous reporting, and clinical laboratory results. The 2 formulations were considered to have met the requirements for bioequivalence if the 90% CIs for the log-transformed C(max) and AUC values were within the predetermined ranges of 75% to 133% and 80% to 125%, respectively, according to the guidelines of the State Food and Drug Administration (SFDA) of China.
All 22 volunteers (mean [SD] age, 22.2 [1.98] years; weight, 64.07 [5.93] kg; height, 173 [5] cm; and body mass index, 21.2 [1.67] kg/m(2)) that were enrolled completed the study. For RIS, the 90% CIs for the ratios of C(max), AUC(0-t), and AUC(0-∞) were 93.2% to 116.7%, 97.9% to 111.3%, and 98.0% to 111.6%, respectively. For 9-OH-RIS, the 90% CIs were 95.8% to 113.9%, 100.2% to 109.7%, and 100.5% to 110.3%, respectively. All values were within the predetermined bioequivalence range. Seven AEs were reported somnolence (4 subjects [9.1%]) and dizziness (3 subjects [6.8%]). All AEs were transient and considered mild by physicians.
The test (dispersible) and reference tablets met the regulatory criteria for bioequivalence as defined by the SFDA. Both formulations were well tolerated. Chinese Clinical Trials registration number: ChiCTR-TRC-12001996.
利培酮（RIS）是一种非典型抗精神病药物，用于治疗成人和儿科人群中与精神分裂症和其他精神障碍相关的精神病。已开发出利培酮的口服分散片制剂。进行这项研究是为了为该药物在中国的营销许可提供支持。
本研究旨在比较两种 RIS 制剂（分散片制剂（试验）和品牌制剂（参比））在健康男性中国志愿者中的药代动力学（PK）特性和生物利用度。
这项单剂量、随机序列、开放标签、两周期交叉研究纳入了 22 名健康的男性中国志愿者。符合条件的参与者被随机分为两组，分别接受试验药物（2mg）或相同剂量的参比制剂，随后进行 2 周的洗脱期和交替制剂给药。在禁食 10 小时后给予研究药物。在给药前和给药后 0.33、0.67、1、1.5、2、3、4、5、6、8、10、12、15、24、36、48、72 和 96 小时采集血样。使用 LC-MS/MS 测量 RIS 和其活性代谢物 9-羟基利培酮（9-OH-RIS）的血浆浓度。通过记录不良事件（AE）、体检（包括生命体征、自发报告和临床实验室结果）评估安全性概况。根据中国国家食品药品监督管理局（SFDA）的指南，如果对数转换后的 Cmax 和 AUC 值的 90%置信区间（CI）分别在 75%至 133%和 80%至 125%的预定范围内，则认为两种制剂符合生物等效性要求。
所有 22 名志愿者（平均[标准差]年龄，22.2[1.98]岁；体重，64.07[5.93]kg；身高，173[5]cm；体重指数，21.2[1.67]kg/m2）均完成了研究。对于 RIS，Cmax、AUC（0-t）和 AUC（0-∞）比值的 90%CI 分别为 93.2%至 116.7%、97.9%至 111.3%和 98.0%至 111.6%。对于 9-OH-RIS，90%CI 分别为 95.8%至 113.9%、100.2%至 109.7%和 100.5%至 110.3%。所有值均在预定的生物等效性范围内。报告了 7 例不良事件（头晕[4 例（9.1%）]和嗜睡[3 例（6.8%）]。所有 AEs 均为一过性，且医生认为均为轻度。
试验（分散片）和参比片剂符合 SFDA 定义的生物等效性监管标准。两种制剂均具有良好的耐受性。中国临床试验注册号：ChiCTR-TRC-12001996。
