He Yan-Ling, Sabo Ron, Campestrini Joelle, Wang Yibin, Riviere Gilles-Jacques, Nielsen Jace C, Rosenberg Mitchell, Ligueros-Saylan Monica, Howard Dan, Dole William P
Novartis Pharmaceuticals, Cambridge, MA, USA.
Br J Clin Pharmacol. 2008 Mar;65(3):338-46. doi: 10.1111/j.1365-2125.2007.03031.x. Epub 2007 Oct 24.
What is already known about this subject. Vildagliptin is a new, potent, and selective inhibitor of DPP-4. The efficacy and safety of vildagliptin in type 2 diabetes has been intensively studied in diverse subject populations. There has been little information published about the pharmacokinetics and pharmacodynamics of vildagliptin. What this study adds. No clinically relevant changes in pharmacokinetics or pharmacodynamics were observed between young and elderly, male and female, or high body mass index (BMI) and low BMI subjects. The results suggest that no dose modification is necessary for vildagliptin based on the age, gender, or BMI of a subject.
To evaluate the effect of age, gender, and body mass index (BMI) on the pharmacokinetics and pharmacodynamics of vildagliptin.
Forty healthy subjects received a single oral dose of 100 mg vildagliptin to assess the effects of age, gender, and BMI on the pharmacokinetics and pharmacodynamics, reflected by the time course of inhibition of DPP-4 activity, of vildagliptin.
Peak concentration and exposure (AUC((0-infinity))) of vildagliptin were 17% (90% CI 2, 35%) and 31% (90% CI 18, 45%) higher in elderly vs. young subjects. Renal clearance was reduced by 32% (90% CI 17, 45%) in elderly subjects. The pharmacokinetics of vildagliptin were not significantly influenced by gender or BMI. Inhibition of DPP-4 activity was similar regardless of age, gender, or BMI.
The pharmacokinetics of a single oral 100 mg dose of vildagliptin were not affected by gender and BMI. Exposure to vildagliptin was higher in elderly patients, but this was not associated with any difference in the effect of DPP-4 inhibition. Based on these results, no vildagliptin dose adjustment is necessary for age, gender, or BMI.
关于该主题已有的认知。维格列汀是一种新型、强效且具有选择性的二肽基肽酶 -4（DPP-4）抑制剂。维格列汀在2型糖尿病患者中的疗效和安全性已在不同人群中进行了深入研究。关于维格列汀的药代动力学和药效学的信息报道较少。本研究的新增内容。在年轻与老年、男性与女性、高体重指数（BMI）与低BMI受试者之间，未观察到维格列汀药代动力学或药效学有临床相关的变化。结果表明，无需根据受试者的年龄、性别或BMI对维格列汀进行剂量调整。
评估年龄、性别和体重指数（BMI）对维格列汀药代动力学和药效学的影响。
40名健康受试者单次口服100mg维格列汀，以评估年龄、性别和BMI对维格列汀药代动力学和药效学的影响，其药效学通过DPP-4活性抑制的时间进程来反映。
与年轻受试者相比，老年受试者维格列汀的峰浓度和暴露量（AUC((0-无穷大))）分别高17%（90%CI 为2, 35%）和31%（90%CI 为18, 45%）。老年受试者的肾清除率降低了32%（90%CI 为17, 45%）。维格列汀的药代动力学不受性别或BMI的显著影响。无论年龄、性别或BMI如何，DPP-4活性的抑制情况相似。
单次口服100mg维格列汀的药代动力学不受性别和BMI的影响。老年患者中维格列汀的暴露量较高，但这与DPP-4抑制效果的差异无关。基于这些结果，无需因年龄、性别或BMI对维格列汀进行剂量调整。
