title: Saxagliptin, a potent, selective inhibitor of DPP-4, does not alter the pharmacokinetics of three oral antidiabetic drugs (metformin, glyburide or pioglitazone) in healthy subjects.
abstract: OBJECTIVE
  To evaluate the pharmacokinetic interactions of the potent, selective, dipeptidyl peptidase-4 inhibitor, saxagliptin, in combination with metformin, glyburide or pioglitazone.
  
  
  METHODS
  To assess the effect of co-administration of saxagliptin with oral antidiabetic drugs (OADs) on the pharmacokinetics and tolerability of saxagliptin, 5-hydroxy saxagliptin, metformin, glyburide, pioglitazone and hydroxy-pioglitazone, analyses of variance were performed on maximum (peak) plasma drug concentration (C(max)), area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) [saxagliptin + metformin (study 1) and saxagliptin + glyburide (study 2)] and area under the concentration-time curve from time 0 to time t (AUC) [saxagliptin + pioglitazone (study 3)] for each analyte in the respective studies. Studies 1 and 2 were open-label, randomized, three-period, three-treatment, crossover studies, and study 3 was an open-label, non-randomized, sequential study in healthy subjects.
  
  
  RESULTS
  Co-administration of saxagliptin with metformin, glyburide or pioglitazone did not result in clinically meaningful alterations in the pharmacokinetics of saxagliptin or its metabolite, 5-hydroxy saxagliptin. Following co-administration of saxagliptin, there were no clinically meaningful alterations in the pharmacokinetics of metformin, glyburide, pioglitazone or hydroxy-pioglitazone. Saxagliptin was generally safe and well tolerated when administered alone or in combination with metformin, glyburide or pioglitazone.
  
  
  CONCLUSIONS
  Saxagliptin can be co-administered with metformin, glyburide or pioglitazone without a need for dose adjustment of either saxagliptin or these OADs.
authors.affiliation: Bristol-Myers Squibb Company, Princeton, NJ, USA. chirag.patel@bms.com
authors.forename: C G
authors.initials: CG
authors.lastname: Patel
authors.forename: D
authors.initials: D
authors.lastname: Kornhauser
authors.forename: N
authors.initials: N
authors.lastname: Vachharajani
authors.forename: B
authors.initials: B
authors.lastname: Komoroski
authors.forename: E
authors.initials: E
authors.lastname: Brenner
authors.forename: M
authors.initials: M
authors.lastname: Handschuh del Corral
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: D W
authors.initials: DW
authors.lastname: Boulton
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004151:Dipeptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005905:Glyburide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D008687:Metformin; C502994:saxagliptin; D000218:Adamantane; D005905:Glyburide; D000077205:Pioglitazone