甲磺酸酚妥拉明口服液的人体生物等效性研究

Study on Bioequivalence of Mesilate Phentolamine Oral Solution in Chinese Healthy Volunteers

目的研究甲磺酸酚妥拉明口服液的人体相对生物利用度和生物等效性。方法健康志愿者20名,随机双交叉单剂量口服武汉同药药业有限公司研制的甲磺酸酚妥拉明口服液(受试制剂,T)和上海东方制药有限公司生产的甲磺酸酚妥枉明分散片(参比制剂,R),剂量均为60 mg,剂间间隔为2周。分别于服药后12 h内多点抽取静脉血;用高效液相色谱法测定血浆中酚妥拉明的浓度。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。AUC0-12,AUC0-inf和ρmax经方差分析和双单侧t检验,tmax进行秩和检验。结果单剂量口服试验和参比制剂后血浆中的酚妥拉明的ρmax分别为(67．365±13．373)和 (67．048±14．341)μg·L-1;tmax分别为(0．438±0．138)和(0．738±0．222)h;AUC0-12分别为(170．711±34．265)和(182．027±．34．594) μg·h·L-1;AUC0-inf分别为(185．836±36．378)和(197．585±36．868)μg·h·L-1。ρmax,AUC0-12和AUC0-inf的90％可信区间分别为 95．5％-105．9％,90．0％-97．4％和90．4％-97．7％。结论试验制剂与参比制剂的人体相对生物利用度为(94．1±9．6)％, 试验制剂与参比制剂具有生物等效性。

OBJECTIVE To study the relative bioavailability and bioequivalence of phentolamine oral solution in healthy volunteers.METHODS A single oral dose （60 mg tested and reference formulation） was given to 20 healthy volunteers in a randomised crossover study. The phentolamine concentrations in plasma were determined by HPLC. The pharmacokinetic parameters were calculated and the bioavailability and bioequivalence of two formulation were evaluated by DAS program. RESULTS After a single dose, the pharmacokinetic parauneters for phentolamine were as follows： ρmax（67.365±13.373） and （67.048±14.341 ）μg·L^-1 ; tmax（0.438±0. 138） and （0.738±0.222）h; AUC0-12（170.711±34.265） and （182.027 ±34.594）μg·h·L^-1; AUC0-inf（185.836±36.378） and （ 197.585±36.868）μg·h·L^-1 for T and R respectively. The 90% confidential intervals of ρmax, AUC0-12 and AUC0-inf of tested formulation were 95.5% -105.9%, 90.0%-97.4% and 90.4%-97.7%, respectively.CONCLUSION The relative bioavailability is （94.1±9.6）%. The results of the statistic analysis show that the two formulations are bioequivalence.