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This Article Full Text Full Text (PDF) All Versions of this Article: 0091270009338938v1 49/10/1210    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Google Scholar Articles by Karim, A. Articles by Mekki, Q. PubMed PubMed Citation Articles by Karim, A. Articles by Mekki, Q. Social Bookmarking                         What's this?

Coadministration of Pioglitazone or Glyburide and Alogliptin: Pharmacokinetic Drug Interaction Assessment in Healthy Participants

From Takeda Global Research & Development Center, Inc, Deerfield, Illinois (Dr Karim, Dr Munsaka, Ms Fleck, Dr Mekki); PPD Development, LP, Austin, Texas (Dr Laurent); and Takeda Pharmaceuticals North America, Inc, Deerfield, Illinois (Dr Wann).

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 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.

Key Words: Pharmacokinetics • drug interaction • oral antidiabetic drugs • alogliptin • pioglitazone • glyburide

Address for reprints: Aziz Karim, PhD, ABCP, FCP, Takeda Global Research & Development Center, Inc, 675 North Field Dr, Lake Forest, IL 60045; e-mail: akarim{at}tgrd.com.

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