He Yan-Ling, Sabo Ron, Riviere Gilles-Jacques, Sunkara Gangadhar, Leon Selene, Ligueros-Saylan Monica, Rosenberg Mitchell, Dole William P, Howard Dan
Exploratory Development, Novartis Institutes for Biomedical Research, Cambridge, MA 02139-3584, USA.
Curr Med Res Opin. 2007 May;23(5):1131-8. doi: 10.1185/030079907x188008.
Vildagliptin is a potent and selective dipeptidyl peptidase-IV (DPP-4) inhibitor that improves glycemic control in patients with type 2 diabetes by increasing alpha and beta-cell responsiveness to glucose. This study assessed the effect of multiple doses of vildagliptin 100 mg once daily on warfarin pharmacokinetics and pharmacodynamics following a single 25 mg oral dose of warfarin sodium.
Open-label, randomized, two-period, two-treatment crossover study in 16 healthy subjects.
The geometric mean ratios (co-administration vs. administration alone) and 90% confidence intervals (CIs) for the area under the plasma concentration-time curve (AUC) of vildagliptin, R- and S-warfarin were 1.04 (0.98, 1.11), 1.00 (0.95, 1.04) and 0.97 (0.93, 1.01), respectively. The 90% CI of the ratios for vildagliptin, R- and S-warfarin maximum plasma concentration (Cmax) were also within the equivalence range 0.80-1.25. Geometric mean ratios (co-administration vs. warfarin alone) of the maximum value and AUC for prothrombin time (PT(max), 1.00 [90% CI 0.97, 1.04]; AUC(PT), 0.99 [0.97, 1.01]) and international normalized ratios (INRmax, 1.01 [0.98, 1.05]; AUC(INR), 0.99 [0.97, 1.01]) were near unity with the 90% CI within the range 0.80-1.25. Vildagliptin was well tolerated alone or co-administered with warfarin; only one adverse event (upper respiratory tract infection in a subject receiving warfarin alone) was reported, which was judged not to be related to study medication.
Co-administration of warfarin with vildagliptin did not alter the pharmacokinetics and pharmacodynamics of R- or S-warfarin. The pharmacokinetics of vildagliptin were not affected by warfarin. No dosage adjustment of either warfarin or vildagliptin is necessary when these drugs are co-medicated.
维格列汀是一种强效、选择性二肽基肽酶-IV（DPP-4）抑制剂，通过增强α细胞和β细胞对葡萄糖的反应性来改善2型糖尿病患者的血糖控制。本研究评估了每日一次口服100 mg维格列汀多剂量给药对单次口服25 mg华法林钠后华法林药代动力学和药效学的影响。
对16名健康受试者进行开放标签、随机、两阶段、双治疗交叉研究。
维格列汀、R-华法林和S-华法林血浆浓度-时间曲线下面积（AUC）的几何平均比值（联合给药与单独给药）及90%置信区间（CI）分别为1.04（0.98，1.11）、1.00（0.95，1.04）和0.97（0.93，1.01）。维格列汀、R-华法林和S-华法林最大血浆浓度（Cmax）比值的90%CI也在等效范围0.80-1.25内。凝血酶原时间最大值（PT(max)）和AUC（PT）以及国际标准化比值（INRmax、AUC(INR)）的几何平均比值（联合给药与单独使用华法林）接近1，90%CI在0.80-1.25范围内（PT(max)，1.00 [90%CI 0.97，1.04]；AUC(PT)，0.99 [0.97，1.01]；INRmax，1.01 [0.98，1.05]；AUC(INR)，0.99 [0.97，1.01]）。维格列汀单独使用或与华法林联合使用耐受性良好；仅报告了1例不良事件（单独接受华法林治疗的1名受试者出现上呼吸道感染），判定与研究药物无关。
华法林与维格列汀联合给药不会改变R-或S-华法林的药代动力学和药效学。华法林不影响维格列汀的药代动力学。这两种药物联合使用时，华法林或维格列汀均无需调整剂量。
