摘要
目的进行多剂量单次口服二甲双胍格列吡嗪片人体药动学研究。方法12名健康志愿者分别口服低、中、高剂量的二甲双胍格列吡嗪片,测定二甲双胍和格列吡嗪血浓度,计算其药动学参数。结果低、中、高剂量二甲双胍格列吡嗪片,二甲双胍主要药动学参数t_(1/2)为(7.09±2.97)h,(5.48±1.84)h和(4.47±1.65)h;T_(max)为(1.69±0.78)h,(1.42±0.42)h和(1.13±0.2)h;C_(max)为(0.42±0.10)μg/ml,(0.76±0.18)μg/ml和(1.28±0.29)μg/ml;AUC_(0-∞)为(3.42±0.56)μg/(ml·h),(4.79±0.69)μg/(ml·h)和(6.90±1.79)μg/(ml·h)。格列吡嗪t_(1/2)为(5.150±2.129)h,(4.948±1.565)h和(5.171±2.568)h;T_(max)为(2.292±0.498)h,(1.917±0.359)h和(2.042±0.334)h;C_(max)为(226.216±63.163)ng/ml,(440.704±149.767)ng/ml和(656.819±190.531)ng/ml;AUC_(0-∞)为(1349.182±760.124)ng/(ml·h),(2433.784±1047.196)ng/(ml·h)和(3546.068±1532.849)ng/(ml·h)。结论二甲双胍和格列吡嗪C_(max)和AUC显示良好剂量相关性,试验过程顺利,低、中、高剂量均未见不良反应发生,二甲双胍格列吡嗪片有良好耐受性。
Objective To study the pharmacokinetics of metformin and glipizide after single dose met- formin-glipizide tablets in Chinese healthy volunteers.Methods Different dosage of metformin-glipizide tablets were given in a orthogonal design test.HPLC-UV and LC-MS methods were established to determine the concen- trations of metformin and gilpizide in plasma. The pharmacokinetic parameters were calculated. Results The main pharmacokinetic parameters of metformin were as follows:t_(1/2)(h)(7.09±2.97),(5.48±1.84)and (4.47±1.65),T_(max)(h)(1.69±0.78),(1.42±0.42)and(1.13±0.2),C_(max)(μg/ml)(0.42±0.10), (0.76±0.18)and(1.28±0.29),AUC_(0-∞)μg/(ml·h)(3.42±0.56),(4.79±0.69)and(6.90±1.79), respectively;of glipizide were as follows:t_(1/2)(h)(5.150±2.129),(4.948±1.565)and(5.171±2.568),T_(max) (h)(2.292±0.498),(1.917±0.359)and (2.042±0.334),C_(max)(ng/ml) (226.216±63.163),(440.704±149.767)and(656.819±190.531),AUC_(0-∞).ng/(ml·h)(1349.182±760.124),(2433.784±1047.196)and(3546.068±1532.849),respectively.Conclusion The C_(max) and AUC of metfomin and glipiz- ide showed better dose dependability.The whole procedure was successful with no adverse effects.
出处
《中国现代药物应用》
2007年第6期12-14,共3页
Chinese Journal of Modern Drug Application
