多潘立酮口崩片的人体生物等效性

Study of the bioequivalence of domperidone orally disintegrating tablets in Chinese healthy volunteers

目的：研究多潘立酮口崩片的人体相对生物利用度和生物等效性。方法：健康志愿者18名，随机双交叉单剂量口服多潘立酮口崩片和多潘立酮片，剂量分别为20mg，剂间间隔为2周。分别于服药后36h内多点抽取静脉血；用高效液相色谱（HPLC）法测定血浆中多潘立酮的质量浓度。用DAS药动学程序计算相对生物利用度并评价两种制剂生物等效性。AUG0-36，AUG0-inf和Cmax经方差分析和双单侧t检验，Tmax进行秩和检验。结果：单剂量口服试验和参比制剂后血浆中的多潘立酮的Cmax分别为（31．0±5．5）μg·L^-1和（33．7±10．8）μg·L^-1；k。分别为（0．56±0．14）h和（0．63±0．13）h；AUC0-36分别为（204．2±85．0）μg·h·L^-1（186．8±58．6）μg·h·L^-1；AUC0-inf分别为（244．8±114．1）μg·h·L^-1和（215．4±56．5）μg·h·L^-1。Cmax、AUC0-36和AUC0-inf的90％可信区间分别为86．3％～104．8％，96．2％～116．5％和94．4％～120．8％。结论：试验制荆与参比制剂的人体相对生物利用度为（108．5±25．1）％，两种制剂具有生物学等效性。

OBJECTIVE To study the relative bioavailability and bioequivalence of domperidone orally disintegrating tablets in healthy volunteers. METItODS A single oral dose （20 mg of test and reference formulation） were given to 18 healthy volunteers in a randomised crossover study. The concentrations of domperidone in plasma were determined by HPLC. The pharmacokinetics parameters were calculated and the bioavailability and bioequivalence of two formulations were evaluated by DAS program. RESULTS After a single dose, the pharmacokinetics parameters for domperidone were as follows： Cmax were （31.0 μ± 5. 5）μg·L^-1 and （33. 7 ± 10. 8）μg·L^-1 ; Tmax were （0. 56± 0. 14） h and （0. 63 ± 0. 13） h;AUC（0-36） were （204. 2 ± 85.0）μg·L^-1 and （186. 8 ± 58. 6）μg·L^-1 ;AUC（0-inf） were （244.8± 114. 1）μg·L^-1 and （215. 4± 56. 5）μg·L^-1 for T and R respectively. The 90% confidential interval of Cmax.AUC（0-36）and AUC（0-inf） of the test formulation were 86. 3 - 104. 8%, 96. 2 - 116. 5 % and 94. 4-120. 8% respectively. CONCLUSION The relative bioavailability is （108. 5 ± 25. 1 ）%; The results of the statistic analysis show that the two formulations are bioequivalent.