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薬理と治療
Abstract
Background Anagliptin is a novel dipeptidyl peptidase-4(DPP-4)inhibitor, whose efficacy and safety have been evaluated in nonclinical studies. In this study, we investigated the pharmacokinetic and pharmacodynamic properties of single and multiple doses of anagliptin in healthy volunteers. Methods Single dose(10-400 mg)or 7-day doses(200 mg twice a day)of anagliptin were administered orally to healthy Japanese volunteers. Pharmacokinetic and pharmacodynamic parameters were measured and investigated. Additionally, the influence of meal on the pharmacokinetics of anagliptin was determined using the 2-period crossover design. Results Administration of a single dose of anagliptin 10 to 400 mg under fasting condition showed a maximum concentration(Cmax)of 58 to 3330 ng/mL and area under the curve (AUC)0- ∞ of 202 to 12600 ng・h/mL, which increased in a dose-dependent manner. The concentration of the major inactive metabolite of anagliptin, SKL-12320, also increased in a dose-dependent manner of anagliptin. The total amount of anagliptin and SKL-12320 excreted into the urine was 55.4 to 69.6%. Anagliptin inhibited plasma DPP-4 activity in a dose-dependent manner and increased the plasma concentration of active glucagon-like peptide-1(GLP-1). Administration of multiple doses of anagliptin showed similar trends of pharmacokinetic and pharmacodynamic profiles as a single dose administration. Meal had no appreciable effect on the pharmacokinetic profile of anagliptin. We did not observe any clinically important adverse events. Conclusions The current pharmacokinetic and pharmacodynamic studies demonstrated favorable efficacy and safety profiles of anagliptin. These results indicate that anagliptin is expected to be an effective drug for diabetes.
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