title: Coadministration of pioglitazone or glyburide and alogliptin: pharmacokinetic drug interaction assessment in healthy participants.
abstract: Alogliptin is a dipeptidyl peptidase-4 inhibitor under investigation for treatment of patients with type 2 diabetes mellitus. Potential pharmacokinetic (PK) drug-drug interactions of alogliptin with pioglitazone or glyburide were evaluated in healthy adults. In a randomized, 6-sequence, 3-period crossover study (study I), participants (n = 30 enrolled; n = 27 completed) received monotherapy with pioglitazone 45 mg once daily (qd), alogliptin 25 mg qd, or coadministration of the 2 agents. The 12-day treatment periods were separated by a > or =10-day washout interval. In a nonrandomized, single-sequence study (study II), participants (n = 24 completed) received a single 5-mg dose of the sulfonylurea glyburide, alone and after 8 days of dosing with alogliptin 25 mg qd. Sequential samples of blood (both studies) and urine (first study) were obtained for determination of PK parameters for alogliptin, pioglitazone, their metabolites, and glyburide. Minor changes in PK parameters between combination therapy and monotherapy were obtained but not judged to be clinically relevant. The combination treatments were well tolerated, although glyburide frequently caused hypoglycemia. Most adverse events were of mild intensity and occurred with a frequency similar to that with monotherapy. It is concluded that pioglitazone or glyburide can be administered with alogliptin without dose adjustment to any component of the combination therapy.
authors.affiliation: Takeda Global Research & Development Center, Inc, Deerfield, IL, USA. akarim@tgrd.com
authors.forename: Aziz
authors.initials: A
authors.lastname: Karim
authors.forename: Aziz
authors.initials: A
authors.lastname: Laurent
authors.forename: Melvin
authors.initials: M
authors.lastname: Munsaka
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wann
authors.forename: Penny
authors.initials: P
authors.lastname: Fleck
authors.forename: Qais
authors.initials: Q
authors.lastname: Mekki
mesh_terms: D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005905:Glyburide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D007004:Hypoglycemic Agents; D010880:Piperidines; D045162:Thiazolidinediones; D014498:Uracil; C520853:alogliptin; D005905:Glyburide; D000077205:Pioglitazone