title: Evaluation of pharmacokinetic and pharmacodynamic interactions of canagliflozin and teneligliptin in Japanese healthy male volunteers.
abstract: OBJECTIVE
  To investigate the pharmacokinetic/pharmacodynamic interactions of the antidiabetic agents canagliflozin (a sodium-glucose cotransporter-2 inhibitor) and teneligliptin (a dipeptidyl peptidase-4 inhibitor) in Japanese healthy adult men.
  
  
  METHODS
  Open-label, one-way crossover study used canagliflozin (200 mg/day p.o.) and teneligliptin (40mg/day p.o). A single dose of object drug (either canagliflozin or teneligliptin) was administered on day 1 followed by washout and continuous administration of precipitant drug (days 1 - 9). Both drugs were concomitantly administered on day 7.
  
  
  RESULTS
  No changes in AUC0 - 72h and Cmax were observed for canagliflozin+teneligliptin versus monotherapy; geometric mean ratios for AUC0 - 72h and Cmax were 0.982 and 0.982 for the plasma concentration of canagliflozin and 0.983 and 0.976 for the plasma concentration of teneligliptin, respectively. Plasma concentrations of active and total glucagon-like peptide-1 (GLP-1) increased with canagliflozin+teneligliptin versus teneligliptin alone. Mean AUC0.5 - 4h increased post-meal, on combination therapy, from 9.6 to 12.5 pmol·h/l (active GLP-1) and from 21.5 to 32.3 pmol·h/l (total GLP-1). Adverse events developed in four subjects; all were mild and resolved but one subject withdrew due to generalized erythema.
  
  
  CONCLUSIONS
  GLP-1 levels increased with the canagliflozin+teneligliptin combination, and no PK interaction was observed. This combination may show favorable antidiabetic effects without increasing systemic exposure.
authors.affiliation: Department of Clinical Pharmacology, Development Division, Mitsubishi Tanabe Pharma Corporation , 17-10 Nihonbashi-Koamicho, Chuo-ku, Tokyo 103-8405 , Japan +81 3 6748 7763 ; +81 3 3663 6449 ; Kinoshita.Shuji@mc.mt-pharma.co.jp.
authors.forename: Shuji
authors.initials: S
authors.lastname: Kinoshita
authors.forename: Kazuoki
authors.initials: K
authors.lastname: Kondo
mesh_terms: D000328:Adult; D044466:Asian People / Q000208:ethnology; D000068896:Canagliflozin; D018592:Cross-Over Studies; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004341:Drug Evaluation / Q000379:methods; D004347:Drug Interactions / Q000502:physiology; D005960:Glucosides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D011720:Pyrazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D053778:Thiazolidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013876:Thiophenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: C579035:3-(4-(4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl)pyrrolidin-2-ylcarbonyl)thiazolidine; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004338:Drug Combinations; D005960:Glucosides; D011720:Pyrazoles; D053778:Thiazolidines; D013876:Thiophenes; D000068896:Canagliflozin
keywords: DPP-4 inhibitor; SGLT2 inhibitor; canagliflozin; drug-drug interaction; teneligliptin