目的 研究伊潘立酮片在中国健康受试者空腹和高脂条件下体内的药动学特征并评价生物等效性。方法 采用开放、随机、两周期、两序列自身交叉试验设计,健康受试者分别空腹和餐后口服1 mg伊潘立酮片受试制剂与参比制剂,采集不同时间点的血样。利用液相色谱-质谱联用法检测血浆样品中伊潘立酮及其代谢物羟基伊潘立酮(P88)的浓度,用PhoenixTMWinNonlin 7.0软件计算两制剂的主要药动学参数,并评价两制剂的生物等效性。结果 空腹状态下,健康受试者口服伊潘立酮片受试制剂和参比制剂后血浆中伊潘立酮和其代谢物P88的ρmax、AUC0-t、AUC0-∞的几何均值比的90%置信区间分别为89.88%~106.61%和90.05%~102.45%、99.81%~109.40%和100.79%~108.17%、100.06%~110.20%和101.58%~110.97%。餐后状态下,血浆中伊潘立酮和P88的ρmax、AUC0-t、AUC0-∞的几何均值比的90%置信区间分别为102.06%~118.14%和100.73%~111.20%、103.94%~111.83%和104.88%~112.29%、104.02%~113.02%和103.29%~111.33%。伊潘立酮受试制剂及参比制剂在空腹和餐后状态下的ρmax、AUC0-t和AUC0-∞的几何均值比的90% 置信区间均在80.00%~125.00%的范围内。结论 伊潘立酮受试制剂和参比制剂在中国健康受试者空腹和餐后状态下均具有生物等效性。
Abstract
OBJECTIVE To study the pharmacokinetics and bioequivalence of iloperidone tablets in Chinese healthy subjects under fasting and fed conditions. METHODS An open, randomized, single-dose, double-period, two-sequence and self-crossover design was adopted. Thirty-six Chinese healthy subjects were randomly divided into two groups under fasting and fed conditions. Blood samples were collected at different time points from the subjects after taking a single dose of 1 mg iloperidone test tablets (T) or reference tablets (R) orally. The concentrations of iloperidone and its metabolite P88 in plasma samples were determined by liquid chromatography-mass spectrometry (LC-MS/MS). The main pharmacokinetic parameters of the two preparations were calculated by PhoenixTM WinNonlin 7.0 software, and the bioequivalence of the two preparations was evaluated. RESULTS Under fasting conditions, the 90% confidence intervals of ρmax, AUC0-t and AUC0-∞ of plasma iloperidone were 89.88%-106.6%, 99.81%-109.40% and 100.06%-110.20%, respectively; the 90% confidence intervals of ρmax, AUC0-t and AUC0-∞ of its metabolite P88 were 90.05%-102.45%, 100.79%-108.17% and 101.58%-110.97%. Under fed conditions, the 90% confidence intervals of ρmax, AUC0-t and AUC0-∞ of plasma iloperidone were 102.06%-118.14%, 103.94%-111.83% and 104.02%-113.02%, respectively; the 90% confidence intervals of ρmax, AUC0-t and AUC0-∞ of its metabolite P88 were100.73%-111.20%, 104.88%-112.29% and 103.29%-111.33%. The 90% confidence intervals of the T:R ratios of ρmax, AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00%-125.00% under fasting and fed conditions. CONCLUSION The test preparation and reference preparation of iloperidone tablets were bioequivalent in Chinese healthy subjects under fasting and fed conditions.
关键词
伊潘立酮 /
羟基伊潘立酮 /
生物等效性 /
药动学
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Key words
iloperidone /
hydroxy iloperidone /
bioequivalence /
pharmacokinetics
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中图分类号：
R969.1
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脚注
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基金
国家科技重大专项重大新药创制项目资助(2020ZX09201-009)
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