Bristol-Myers Squibb Company, Princeton, NJ, USA.
Diabetes Obes Metab. 2011 Jul;13(7):604-14. doi: 10.1111/j.1463-1326.2011.01381.x.
To evaluate the pharmacokinetic interactions of the potent, selective, dipeptidyl peptidase-4 inhibitor, saxagliptin, in combination with metformin, glyburide or pioglitazone.
To assess the effect of co-administration of saxagliptin with oral antidiabetic drugs (OADs) on the pharmacokinetics and tolerability of saxagliptin, 5-hydroxy saxagliptin, metformin, glyburide, pioglitazone and hydroxy-pioglitazone, analyses of variance were performed on maximum (peak) plasma drug concentration (C(max)), area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) [saxagliptin + metformin (study 1) and saxagliptin + glyburide (study 2)] and area under the concentration-time curve from time 0 to time t (AUC) [saxagliptin + pioglitazone (study 3)] for each analyte in the respective studies. Studies 1 and 2 were open-label, randomized, three-period, three-treatment, crossover studies, and study 3 was an open-label, non-randomized, sequential study in healthy subjects.
Co-administration of saxagliptin with metformin, glyburide or pioglitazone did not result in clinically meaningful alterations in the pharmacokinetics of saxagliptin or its metabolite, 5-hydroxy saxagliptin. Following co-administration of saxagliptin, there were no clinically meaningful alterations in the pharmacokinetics of metformin, glyburide, pioglitazone or hydroxy-pioglitazone. Saxagliptin was generally safe and well tolerated when administered alone or in combination with metformin, glyburide or pioglitazone.
Saxagliptin can be co-administered with metformin, glyburide or pioglitazone without a need for dose adjustment of either saxagliptin or these OADs.
评估强效、选择性二肽基肽酶-4 抑制剂沙格列汀与二甲双胍、格列吡嗪或吡格列酮联合应用的药代动力学相互作用。
为评估沙格列汀与口服降糖药（OAD）联合应用对沙格列汀、5-羟基沙格列汀、二甲双胍、格列吡嗪和羟吡格列嗪药代动力学和耐受性的影响，对各研究中每个分析物的最大（峰）血浆药物浓度（C(max)）和零时间至无穷大（AUC(∞)）时的血浆浓度-时间曲线下面积（saxagliptin + metformin [研究 1] 和 saxagliptin + glyburide [研究 2]）及从 0 时间至 t 时间（AUC）时的浓度-时间曲线下面积（saxagliptin + pioglitazone [研究 3]）进行方差分析。研究 1 和 2 为开放标签、随机、三周期、三处理、交叉研究，研究 3 为健康受试者的开放标签、非随机、序贯研究。
沙格列汀与二甲双胍、格列吡嗪或吡格列酮联合应用并未导致沙格列汀或其代谢物 5-羟基沙格列汀的药代动力学出现有临床意义的改变。沙格列汀联合应用后，二甲双胍、格列吡嗪、吡格列酮或羟吡格列酮的药代动力学无临床意义的改变。沙格列汀单独或与二甲双胍、格列吡嗪或吡格列酮联合应用时通常安全且耐受良好。
沙格列汀可与二甲双胍、格列吡嗪或吡格列酮联合应用，无需调整沙格列汀或这些 OAD 的剂量。
