奥卡西平片的人体相对生物利用度研究

Relative Bioavailability of Oxcarbazepine Tablets in Healthy Volunteers

目的 :研究国产奥卡西平片的人体相对生物利用度和生物等效性。方法 :健康志愿者 2 0名 ,随机双交叉单剂量口服试验和参比的奥卡西平片 ,剂量为 30 0mg ,剂间间隔为 2周。分别于服药后 4 8h内多点抽取静脉血。用高效液相色谱法 (HPLC)测定血浆中奥卡西平的活性代谢物MHD的浓度。结果 :MHD的线性范围为 0 .10～ 10 .0 0mg/L ,最低检测浓度为 0 .10mg/L ,方法的平均回收率为 (99.4± 4 .2 ) %。 2 0名志愿者随机交叉口服单剂量两种制剂后 ,MHD的cmax分别为 4 .6 1± 0 .5 7mg/L和 16 .34± 5 .2 9mg/L ;tmax分别为 4 .6 5± 2 .74h和 4 .2 0± 2 .0 2h ;t1/2 (Ke) 分别为 16 .5 7± 4 .0 1h和 16 .34± 5 .2 9h ;AUC( 0 48) 分别为 10 0 .2 4± 16 .6 2mg·h/L和 97.97± 19.0 1mg·h/L ;AUC( 0 inf) 分别为 118.93± 4 .6 1mg·h/L和 115 .4 3± 4 .6 4mg·h/L。试验制剂与参比制剂的相对生物利用度F =(10 3.4± 10 .5 ) %。AUC( 0 48) ,cmax,tmax均无显著性差异。结论 :该方法简便、准确、灵敏度高 ;两种制剂生物学等效。

AIM:To study the bioequivalence and relative bioavailability of domestic Oxcarbazepine tablets.METHOD:A single oral dose (300 mg of tested and reference formulation) was given to 20 healthy volunteers in a randomised crossover study. The plasma concentrations of the active metabolite (10-monohydroxy carbamazepine, MHD) of Oxcarbazepine were determined by RP-HPLC method. The pharmacokinetics parameters were calculated and the bioavailability and bioequivalence of two formulations were evaluated.RESULT:The calibration curve was liner over the range of 0.10～10.00 mg/L and the detection limit was 0.10 mg/L. The average recovery of the method was (99.4±4.2)%. After a single dose, the pharmacokinetics parameters for MHD were as follows: c _ max were 4.61±0.57 mg/L and 16.34±5.29 mg/L; t _ max were 4.65±2.74 h and 4.20±2.02 h; t _ 1/2 were 16.57±4.01 h and 16.34±5.29 h;AUC_ (0-48) were 100.24±16.62 mg·h/L and 97.97±19.01 mg·h/L;AUC_ (0-inf) were 118.93±4.61 mg·h/L and 115.43±4.64 mg·h/L for T and R respectively;the relative bioavailability was (103.4±10.5)%.CONCLUSION:The method is simple, sensitive and rapid. The results of the statistic analysis showed that the two formulations were bioequivalent.