多潘立酮口腔崩解片在健康人体的药动学和生物等效性

目的:建立液-质联用测定人血浆中多潘立酮的浓度,研究多潘立酮口腔崩解片与多潘立酮片的人体药动学及相对生物利用度。方法:血浆样品中加入内标盐酸苯海拉明,经甲醇沉淀蛋白,采用液-质联用测定。用建立的方法测定18例男性健康志愿者单剂量口服受试制剂(多潘立酮口腔崩解片)或参比制剂(多潘立酮片)后的血药浓度,求得药动学参数,并对2种制剂的生物等效性进行评价。结果:在0.100～50 ng·mL-1内呈良好的线性关系,方法回收率79.2%～87.8%,日内、日间RSD均小于15%。单次口服10 mg受试制剂或参比制剂后的Cmax分别为(20.5±7.6)和(15.8±6.1)ng·mL-1;tmax分别为(0.79±0.21)和(0.68±0.31)h;t1/2分别为(9.92±2.02)和(9.50±1.61)h;AUC(0-36)分别为(84.3±26.2)和(71.0±15.0)h·ng·mL-1;AUC(0-∞)分别为(89.8±28.2)和(74.6±16.4)h·ng·mL-1。受试制剂对参比制剂的相对生物利用度为(113.5±10.3)%。结论:该方法灵敏,无杂质干扰。测得的受试制剂与参比制剂的主要药动学参数之间无明显差异,表明2种制剂在人体内生物等效。

Pharmacokinetics and bioequivalence of domperidone orally disintegrating tablets in healthy volunteers

OBJECTIVE To determine domperidone in human plasma by LC-MS/MS method,and to investigate its pharmacokinetics and relative bioavailability.METHODS Domperidone concentrations in plasma extracted with being precipitated protein by methanol were determinated by LC-MS/MS.The test formulations(domperidone orally disintegrating tablets)and reference formulations(domperidone tablets) were given to 18 healthy male volunteers.The pharmacokinetics of test formulations(domperidone orally disin-tegrating tablets) and reference formulations and the bioequivalence of the two formulations were evaluated.RESULTS The calibration curve was linear within the range of 0.100-50 ng·mL-1.The method recovery was 79.2%-87.8%.RSDs of intra-day and inter-day were less than 15%.After a single oral dose of 10 mg the test or reference formulations,the main pharmacokinetic parameters were as follows: Cmax(20.5±7.6) and(15.8±6.1) ng·mL-1;tmax(0.79±0.21) and(0.68±0.31)h;t1/2(9.92±2.02) and(9.50±1.61)h;AUC(0-36)(84.3±26.2) and(71.0±15.0)h·ng·mL-1;AUC(0-∞)(89.8±28.2) and(74.6±16.4)h·ng·mL-1,respectively.Relative bioavailability was(113.5±10.3)%.CONCLUSION The method was sensitive with no endogenous interference.No significant difference exists among the main pharmacokinetic parameters for the test and reference tablets.The two formulations are bioequivalence.