Mistry Goutam C, Bergman Arthur J, Zheng Wei, Hreniuk David, Zinny Miguel A, Gottesdiener Keith M, Wagner John A, Herman Gary A, Ruddy Marcella
Merck & Co., Inc., Whitehouse Station, NJ, USA.
Br J Clin Pharmacol. 2008 Jul;66(1):36-42. doi: 10.1111/j.1365-2125.2008.03148.x. Epub 2008 May 22.
Sitagliptin, a dipeptidyl peptidase-4 inhibitor, is an incretin enhancer that is approved for the treatment of Type 2 diabetes. Sitagliptin is mainly renally eliminated and not an inhibitor of CYP450 enzymes in vitro. Glyburide, a sulphonylurea, is an insulin sensitizer and mainly metabolized by CYP2C9. Since both agents may potentially be co-administered, the purpose of this study was to examine the effects of sitagliptin on glyburide pharmacokinetics.
In this open-label, randomized, two-period crossover study, eight healthy normoglycaemic subjects, 22-44 years old, received single 1.25-mg doses of glyburide alone in one period and co-administered with sitagliptin on day 5 following a multiple-dose regimen for sitagliptin (200-mg q.d. x 6 days) in the other period.
The geometric mean ratios and 90% confidence intervals [(glyburide + sitagliptin)/glyburide] for AUC(0-infinity) and C(max) were 1.09 (0.96, 1.24) and 1.01 (0.84, 1.23), respectively.
Sitagliptin does not alter the pharmacokinetics of glyburide in healthy subjects.
西他列汀是一种二肽基肽酶-4抑制剂，是一种肠促胰岛素增强剂，已被批准用于治疗2型糖尿病。西他列汀主要经肾脏排泄，在体外不是细胞色素P450酶的抑制剂。格列本脲是一种磺酰脲类药物，是一种胰岛素增敏剂，主要通过细胞色素P450 2C9代谢。由于这两种药物可能会联合使用，本研究的目的是考察西他列汀对格列本脲药代动力学的影响。
在这项开放标签、随机、两周期交叉研究中，8名年龄在22至44岁之间的健康血糖正常受试者，在一个周期内单独接受1.25 mg的格列本脲单剂量给药，在另一个周期内，在西他列汀多剂量给药方案（200 mg，每日一次，共6天）后的第5天，与西他列汀联合给药。
AUC(0-∞)和C(max)的几何平均比值及90%置信区间[（格列本脲+西他列汀）/格列本脲]分别为1.09（0.96，1.24）和1.01（0.84，1.23）。
在健康受试者中，西他列汀不改变格列本脲的药代动力学。
