Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, No. 966, Huaihai Rd.(M), Shanghai, 200031, China.
Sumitomo Pharmaceuticals (Suzhou) Co. Ltd., Beijing, China.
Clin Drug Investig. 2017 Sep;37(9):861-871. doi: 10.1007/s40261-017-0546-8.
The pharmacokinetics of lurasidone have been studied in healthy Japanese and Caucasian subjects, but not in Chinese subjects. The objective of this study was to evaluate the pharmacokinetics, safety, and tolerability of oral lurasidone in healthy Chinese subjects.
This single-center, randomized, parallel-group, placebo-controlled, and double-blind study evaluated the pharmacokinetics, safety, and tolerability of oral lurasidone administered as a single dose (20, 40, and 80 mg) and multiple doses for 5 days (40 mg administered once daily) in healthy Chinese subjects. Serum lurasidone and its metabolites were quantified using high-performance liquid chromatography-mass spectrometry. Pharmacokinetic parameters for lurasidone and its metabolites were calculated using non-compartmental analysis of WinNonlin version 6.2. Safety analyses were recorded using physical examinations, vital signs, electrocardiogram, and clinical laboratory tests.
Serum concentrations of lurasidone reached maximum concentration (C ) within 1.0-3.0 h after each single dose, and then decreased biphasically, with a mean half-life (t ) from 18.1 to 25.5 h over the dose range of 20-80 mg. The area under the concentration-time curve (AUC) and C values increased approximately dose proportionally. Lurasidone steady state was achieved after 5 days of daily dosing and the accumulation index of the AUC during a dosage interval (AUC) was 1.25, smaller than theoretical cumulative coefficient (1.76). Similar results were observed for the metabolites (ID-14283, ID-14326, and ID-11614). No severe adverse events (AEs) were observed in the single- or multiple-dose studies and no subject discontinued from the study due to AEs. The most common reported AEs were somnolence, increased blood prolactin, and restlessness, with a higher rate as dose increased.
Lurasidone was safe and well-tolerated in healthy Chinese subjects, following single doses in the range of 20 to 80 mg and multiple doses of 40 mg/day for 5 days. Linear increase in lurasidone C and AUC values were seen following single doses from 20 to 80 mg. There was no unexpected accumulation after multiple administrations of lurasidone at 40 mg/day, and the pharmacokinetic characteristics were consistent with the conclusion obtained in the previous studies.
Clinicaltrials.gov identifiers NCT02174510 and NCT02174523.
卢拉西酮的药代动力学已在健康的日本和白种人群体中进行了研究，但尚未在中国人群体中进行研究。本研究的目的是评估口服卢拉西酮在健康中国受试者中的药代动力学、安全性和耐受性。
这项单中心、随机、平行组、安慰剂对照、双盲研究评估了口服卢拉西酮单剂量（20、40 和 80mg）和 5 天（40mg 每日一次）多剂量在健康中国受试者中的药代动力学、安全性和耐受性。使用高效液相色谱-质谱法定量血清卢拉西酮及其代谢物。使用非房室分析的 WinNonlin 版本 6.2 计算卢拉西酮及其代谢物的药代动力学参数。使用体格检查、生命体征、心电图和临床实验室检查记录安全性分析。
单次给药后 1.0-3.0 小时内，血清卢拉西酮浓度达到最大浓度（C ），然后呈双相下降，20-80mg 剂量范围内平均半衰期（t ）为 18.1-25.5 小时。浓度-时间曲线下面积（AUC）和 C 值与剂量呈近似比例增加。每日给药 5 天后达到卢拉西酮稳态，AUC 剂量间隔内的蓄积指数（AUC）为 1.25，小于理论累积系数（1.76）。代谢物（ID-14283、ID-14326 和 ID-11614）也观察到类似的结果。在单剂量或多剂量研究中均未观察到严重不良事件（AE），也没有受试者因 AE 而退出研究。最常见的报告 AEs 是嗜睡、催乳素升高和不安，随着剂量的增加发生率更高。
卢拉西酮在健康的中国受试者中安全且耐受良好，单剂量范围为 20-80mg，连续 5 天每日 40mg 多剂量。单剂量从 20 至 80mg 时，卢拉西酮 C 和 AUC 值呈线性增加。每日 40mg 多次给药后无意外蓄积，药代动力学特征与先前研究的结论一致。
Clinicaltrials.gov 标识符 NCT02174510 和 NCT02174523。
