He Yan-Ling, Sabo Ron, Sunkara Gangadhar, Bizot Marie-Noëlle, Riviere Gilles-Jacques, Leon Selene, Ligueros-Saylan Monica, Dole William P, Howard Dan
Exploratory Development-DMPK, Novartis Institutes for Biomedical Research, 400 Technology Square, Building 605, Cambridge, MA 02139-3584, USA.
J Clin Pharmacol. 2007 Aug;47(8):998-1004. doi: 10.1177/0091270007301802.
Vildagliptin is a novel antidiabetic agent that is an orally active, potent, and selective inhibitor of dipeptidyl peptidase IV, the enzyme responsible for degradation of the incretin hormones. This open-label, randomized, 3-period crossover study investigated the potential for pharmacokinetic interactions in 18 healthy subjects during coadministration of vildagliptin and digoxin. Subjects were randomized to receive each of 3 treatments: vildagliptin 100 mg qd, digoxin (0.5 mg, then 0.25 mg qd on days 2-7), and the combination vildagliptin/digoxin for 7 days. Coadministration of digoxin with vildagliptin had no effect on exposure to vildagliptin (geometric mean ratios [90% confidence interval]: AUC(0-24h), 0.99 [0.95-1.03]; C(max), 0.95 [0.85-1.06]) or to digoxin (AUC(0-24h), 1.02 [0.94-1.12]; C(max), 1.08 [0.97-1.20]). In addition, no changes in t(max), t((1/2)), and CL/F were observed for either drug. These results indicate that no dose adjustment is necessary when vildagliptin and digoxin are coadministered.
维格列汀是一种新型抗糖尿病药物，它是一种口服活性、强效且选择性的二肽基肽酶IV抑制剂，该酶负责肠促胰岛素激素的降解。这项开放标签、随机、3期交叉研究调查了18名健康受试者在同时服用维格列汀和地高辛期间药代动力学相互作用的可能性。受试者被随机接受3种治疗中的每一种：维格列汀100 mg每日一次，地高辛（第1天0.5 mg，第2 - 7天每日0.25 mg），以及维格列汀/地高辛联合用药7天。地高辛与维格列汀同时给药对维格列汀的暴露量（几何平均比值[90%置信区间]：AUC(0 - 24h)，0.99 [0.95 - 1.03]；C(max)，0.95 [0.85 - 1.06]）或地高辛的暴露量（AUC(0 - 24h)，1.02 [0.94 - 1.12]；C(max)，1.08 [0.97 - 1.20]）没有影响。此外，两种药物的t(max)、t((1/2))和CL/F均未观察到变化。这些结果表明，维格列汀和地高辛同时给药时无需调整剂量。
