Pharmacokinetics and metabolism of [14C]anagliptin, a novel dipeptidyl peptidase-4 inhibitor, in humans

Xenobiotica. 2013 May;43(5):432-42. doi: 10.3109/00498254.2012.731618. Epub 2012 Oct 18.

Abstract

1. The disposition of anagliptin, an orally active, highly selective dipeptidyl peptidase-4 inhibitor, was investigated after a single oral dose of 100 mg/1.92 MBq [(14)C]anagliptin to six healthy men. Almost all the dose (98.2%) was recovered within 168 h: 73.2% in urine and 25.0% in faeces. 2. Anagliptin was rapidly absorbed, with peak plasma concentrations of unchanged drug attained at a mean time of 1.8-h postdose. Mean fraction of the dose absorbed was >73%. Unchanged drug and a carboxylate metabolite (M1) were the major components in plasma, accounting for 66.0 and 23.4% of total plasma radioactivity area under the curve, respectively. 3. Anagliptin was incompletely metabolized, with about 50% dose eliminated as unchanged drug (46.6% in urine and 4.1% in faeces). Metabolism to M1 accounted for 29.2% of the dose. No other metabolite accounted for >1% dose in excreta or yielded measurable systemic exposure. Terminal half-life of anagliptin and M1 was 4.37 and 9.88 h, respectively. Renal clearance of unbound anagliptin and unbound M1 far exceeded glomerular filtration rate, indicating active renal elimination: that might reflect the fact that anagliptin may be a substrate of OAT1, OAT3, MDR1 and MRP2, and M1 a substrate of OAT3, BCRP, MRP2 and MRP4.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Carbon Radioisotopes / blood
  • Carbon Radioisotopes / pharmacokinetics
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / blood
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacokinetics*
  • Half-Life
  • Humans
  • Male
  • Pyrimidines / administration & dosage
  • Pyrimidines / blood
  • Pyrimidines / pharmacokinetics*

Substances

  • Carbon Radioisotopes
  • Dipeptidyl-Peptidase IV Inhibitors
  • Pyrimidines
  • anagliptin