目的建立HPLC测定血浆中那格列奈,并研究其药动学及相对生物利用度。方法18名受试者随机等分成2组,先后单剂量po受试制剂或参比制剂后,采用HPLC测定血药浓度,计算药动学参数并进行方差分析,以双单侧t检验进行生物等效性判定。结果单次服用60 mg受试制剂或参比制剂后的药动学参数AUC_0～10,AUC_0～∞,ρ_max,t_max及t_1/2分别为(6.84±3.51)和(7.24±3.51)mg·h·L^-1,(6.95±3.45)和(7.38±3.58)mg·h·L^-1,(4.35±2.45)和(4.20±2.13)mg·L^-1,(1.02±0.48)和(1.16±0.51)h,(2.20±0.78)和(2.04±0.65)h。受试制剂对参比制剂的相对生物利用度为(94.5±13)%。2种制剂的药动学参数无明显差异。结论HPLC能快速、准确测定人血浆中的那格列奈,受试制剂与参比制剂具有生物等效性。

OBJECTIVE To determine the concentration of nateglinide in human plasma by HPLC method,and study its pharmacokinetics,relative bioavailability.METHODS Eighteen volunteers were randomized into 2 groups.The subjects in group one firstly received the test preparation of nateglinide tablets,followed by the reference preparation.The subjects in group two received the reference preparation firstly,followed by the test preparation.The plasma concentration of nateglinide was measured by high performance liquid chromatography(HPLC) method.ANOVA was used to check the difference of the means of the pharmacokinetic parameters between the two preparations.Bioequivalence was determined by student t-tests.RESULTS The pharmacokinetic parameters of the volunteers after a single dose of 60 mg of the test preparation or the reference preparation were as follows:AUC_0～10(6.84±3.51) and(7.24±3.51) mg·h·L^-1,AUC_0～∞(6.95±3.45) and(7.38±3.58) mg·h·L^-1,ρ_max(4.35±2.45) and(4.20±2.13) mg·L^-1,t_max(1.02±0.48) and(1.16±0.51) h,t_1/2(2.20±0.78) and(2.04±0.65) h,respectively.The relative bioavailability was(94.5±13)%.No significant differences were found among the main pharmacokinetic parameters.CONCLUSION The method can determine gemflbrozil in the human body quickly and correctly.The two preparations are equivalent.