盐酸二氧丙嗪颗粒的人体生物等效性研究

Study on Bioequivalence of Dioxopromethazine Hydrochloride Granules in Healthy Volunteers

目的研究盐酸二氧丙嗪颗粒的人体相对生物利用度。方法健康志愿者18名,随机双交叉单剂量口服盐酸二氧丙嗪实验和参比制剂,用高效液相色谱法测定血浆中盐酸二氧丙嗪的浓度。用DAS程序计算相对生物利用度和评价生物等效性。AUC0-60,AUC0-inf和ρmax经方差分析和双单侧t检验,tmax进行秩和检验。结果单剂量口服实验制剂和参比制剂后血浆中的盐酸二氧丙嗪的ρmax分别为（30.548±5.373）和（29.670±4.970）μg·L^-1tmax分别为（2.833±1.225）和（2.593±1.798）h;AUC0-60分别为（436.722±95.713）和（433.668±83.881）μg·h·L^-1AUC0-inf分别为（455.990±105.688）和（448.718±84.741）μg·h·L^-1ρmax,AUC0-60,AUC0-inf的90%可信区间分别为98.0%-107.9%,95.7%-105.0%,95.1%-107.0%。结论试验制剂对参比制剂的人体相对生物利用度为（101.3±15.2）%,试验制剂和参比制剂具有生物等效性。

OBJECTIVE To study the relative bioavailability of Dioxopromethazine Hydrochloride granules in healthy volunteers. METHODS A single oral dose （9 mg of tested and reference formulation） was given to 18 healthy volunteers in a randomized crossover study. The concentrations of Dioxopromethazine Hydrochloride in plasma were determined by HPLC. The pharmacokinetic parameters were calculated and the bioavailability and bioequivalence of two formulations were evaluated by DAS program. RESULTS After a single dose, the pharmacokinetic parameters for Dioxopromethazine Hydrochloride were as follows ： Pmax （ 30. 548 ± 5. 373 ） and （29.670±4.970） μg· L^-1;tmax,（2.833±1.225） and （2.593_±1.798）h; AUCoo （ 436. 722_± 95.713） and （433.668 ± 83.881 ） μg · h · L^-1 ; AUCo- max （455. 990 ± 105. 688 ） and （ 448.718± 84.741 ） μg · h ~ ·L ^- 1 for T and R respectively. The 90% confidential interval ofp AUC0-60 and AUCo0-inf of tested formulation were 98.0% - 107.9% ,95.7% - 105.0% and 95. 1% - 107.0% , respectively. CONCLUSION The relative bioavailability was （ 101.3 ±15.2） %. The results of the statistic analysis showed that the two formulations were bioecmivalence.