西他列汀，一种二肽基肽酶-4抑制剂，在健康受试者中不会改变磺脲类药物格列本脲的药代动力学。
Sitagliptin, an dipeptidyl peptidase-4 inhibitor, does not alter the pharmacokinetics of the sulphonylurea, glyburide, in healthy subjects.
作者信息
Mistry Goutam C, Bergman Arthur J, Zheng Wei, Hreniuk David, Zinny Miguel A, Gottesdiener Keith M, Wagner John A, Herman Gary A, Ruddy Marcella
机构信息
Merck & Co., Inc., Whitehouse Station, NJ, USA.
出版信息
Br J Clin Pharmacol. 2008 Jul;66(1):36-42. doi: 10.1111/j.1365-2125.2008.03148.x. Epub 2008 May 22.
Abstract
AIMS
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.
METHODS
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.
RESULTS
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.
CONCLUSION
Sitagliptin does not alter the pharmacokinetics of glyburide in healthy subjects.
摘要
目的
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。
方法
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。
结果
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）。
结论
在健康受试者中，西他列汀不改变格列本脲的药代动力学。
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