酒石酸唑吡坦口溶片的生物等效性评价

Bioequivalence evaluation of zolpidem tartrate mouth-dissolving tablets

目的建立狗血浆中酒石酸唑吡坦浓度的测定方法 ,评价唑吡坦口溶片与普通唑吡坦片的生物等效性。方法采用高效液相色谱 荧光检测法测定 6条Beagle狗单剂量交叉口服供试品和对照品 10mg后不同时间点的血浆药物浓度 ,观察主要药动学参数是否存在差异 ,测定相对生物利用度 ,并评价 2种制剂的生物等效性。结果供试品和对照品的Tmax分别为 (2 6 .6 7± 14 .72 )、(41.6 7± 18.0 7)min ,Cmax为 (36 .4 16± 2 0 .2 90 )、(15 .10 0± 5 .6 4 6 )ng ml,AUC0 t为 (2 890 .85± 110 1.0 5 )、(1388.5 8± 4 84 .11)ng·min ml。方差分析结果显示供试品的Cmax与AUC0 t显著大于对照品。双单侧t检验显示供试品与对照品生物不等效。结论供试品与对照品生物不等效。供试品相对生物利用度为 (2 0 9.5 1± 37.93) %。

PurposeTo establish a sensitive method for determination of zolpidem tartrate concentration in Beagle dogs′ plasma and evaluate the bioequivalence of zolpidem mouth-dissolving tablets.MethodsPlasma Zolpidem tartrate concentration was determined by HPLC-FLD method following a single oral dose 10 mg of two zolpidem tartrate formulations to 6 Beagle dogs in an open randomized crossover test. The pharmacokinetics parameters and relative bioavailability were calculated and the bioequivalence between test tablets and reference standard was evaluated by two-one-side t test.ResultsThe T max of test tablets and reference standard were (26.67±14.72) min and (41.67±18.07) min, C max were (36.416±20.290) ng/ml and (15.100±5.646) ng/ml, AUC 0-t were (2 890.85±1 101.05) ng·min/ml and (1 388.58±484.11) ng·min/ml, respectively. C max and AUC 0-t of the test tablet were significantly higher than those of the reference. Two one-side t test showed that the two formulations were not bioequivalent.ConclusionThe test formulation was not bioequivalent to the reference preparation and the relative bioavailability was (209.51±37.93)%.