北京产硫酸吗啡控释片的人体相对生物利用度研究

目的·· :研究正常人单剂量口服北京产硫酸吗啡控释片的人体相对生物利用度 ,及多次给药的稳态血药浓度和波动性。方法·· :正常健康志愿者19例,随机自身交叉口服北京产硫酸吗啡控释片和进口片30mg;晚期癌痛病人27例次 ,随机(部分病人自身交叉)多次口服北京产硫酸吗啡控释片和进口片至稳态。采用GC -MS测定血药浓度。结果··:求得北京产硫酸吗啡控释片和进口片的Cmax 为14.65ng·ml-1±s3.08ng·ml-1 和14.71ng·ml-1±s2.13ng·ml -1,Tmax 为3.84h±s0.50h和3.84h±s0.37h,曲线下面积AUC为76.67ng·h·ml -1±s8.32ng·h·ml-1 和80.06ng·h·ml-1±s10.89ng·h·ml-1,北京产硫酸吗啡控释片的相对生物利用度为96.89%±s15.33 % ;达稳态时谷浓度分别为15.11ng·ml -1±s8.98ng·ml -1和12.52ng·ml -1±s10.14ng·ml -1 ,峰浓度分别为24.06ng·ml -1±s11.18ng·ml -1和20.32ng·ml -1±s13.18ng·ml -1,血药浓度的波动系数( %)为47.96±s19.91和46.89±s18.77。结论··:北京产硫酸吗啡控释片的人体相对生物利用度符合要求 ,多次给药的稳态血药浓度和波动性与进口片无显著性差异。

RELATIVE BIOAVAILABILITY OF DOMESTIC CONTROLLED RELEASE MORPHINE SULPHATE TABLET IN CHINESE VOLUNTEERS

Objective: To study the pharmacokinetics and relative bioavailability of domestic controlled release morphine sulphate tablet. Method: A single oral dose of domestic tablet and MST Continus were given to 19 Chinese healthy volunteers in an open randomized crossover study. The steady-state level of morphine was studied in 27 cancer Chinese patients with sever pain in an open crossover study or parallel controlled trial. The plasma concentration of morphine was determined by GC-MS. Result: After a single dose 30 mg, peak plasma levels (Cmax) of domestic tablet and MST Continus were 14.65 ng·ml-1±s 3.08 ng·ml-1 and 14.71 ng·ml-1±s 2.13 ng·ml-1, Tmax=3.84 h±s 0.50 h and 3.84 h±s 0.37 h, AUC=76.67 ng·h·ml-1±s 8.32 ng·h·ml-1 and 80.06 ng· h· ml-1 ±s 10.89 ng·h·ml-1, respectively. Following multiple doses, Cmin=15.11 ng·ml-1±s 8.98 ng·ml-1 and 12.52 ng·ml-1±s 10.14 ng·ml-1,Cmax=24.06 ng·ml-1±s 11.18 ng· ml-1 and 20.32 ng·ml-1±s 13.18 ng·ml-1, the peak-to-through fluctuation index (FI)was 47.96%±s 19.91% and 46.89%±s 18.77%, respectively. Conclusion: The relative bioavailability of domestic tablet is 96.89%±s 15.33%. There is a bioequivalency in comparison with MST Continus made in England.