降糖药与CVD安全性关注DPP.ppt

DPP-4 Activity Is Inhibited by 97% Over 24 Hours With Sitagliptin 100 mg This graph shows the time profiles for mean plasma DPP-4 inhibition after administration of a single oral dose of sitagliptin 100 mg to healthy subjects. As shown, mean DPP-4 inhibition over 24 hours with sitagliptin 100 mg was 97%.1 The DPP-4 inhibition curve shown here was generated by applying a mathematical correction to previously published sitagliptin results from a single-dose study (5–400 mg) in healthy men.1,2 When corrected for assay and dilutional effects to estimate inhibition of in vivo DPP-4 activity, corrected weighted average percent DPP-4 inhibition values were increased relative to the uncorrected values at the respective doses. As the dose increased, the increment for the difference between the corrected and uncorrected values became smaller, suggesting that the top of the dose-response curve was achieved. This was consistent with the sigmoidal relationship between plasma sitagliptin and DPP-4 inhibition, in which plasma concentrations ≥100 nM observed with sitagliptin doses ≥100 mg provided DPP-4 inhibition over 24 hours.1 Purpose To show the mean plasma DPP-4 inhibition after single-dose administration of sitagliptin 100 mg to healthy subjects. Takeaway Mean corrected inhibition of DPP-4 activity over 24 hours is 97%. References 1. Alba M, Sheng D, Guan Y, et al. Sitagliptin 100 mg daily effect on DPP-4 inhibition and compound-specific glycemic improvement. Curr Med Res Opin. 2009;25(10):2507–2514. Electronic supplementary data published in conjunction with Alba M, Sheng D, Guan Y, et al. Curr Med Res Opin. 2009;25(10):2507–2514. doi: 10.1185/03007990902109514. 2. Herman GA, Stevens C, Van Dyck K et al. Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharmacol Ther. 2005;78:675–688. Alba 2009(o