Evaluation of the pharmacokinetic interaction between the dipeptidyl peptidase-4 inhibitor linagliptin and pioglitazone in healthy volunteers
E.U. Graefe-Mody1, A. Jungnik1, A. Ring1, H.J. Woerle1, K.A. Dugi2
1 Boehringer Ingelheim Pharma GmbH and Co. KG, Biberach/Riss, and 2 Boehringer Ingelheim GmbH, Ingelheim, Germany
DOI 10.5414/CPP48652
Abstract
Objective: Co-administration of the dipeptidyl peptidase-4 inhibitor linagliptin (BI 1356) with pioglitazone may improve glycemic control in patients with Type 2 diabetes due to their complementary mechanisms of action. This study aimed to investigate any potential pharmacokinetic interaction between linagliptin and pioglitazone, a CYP 2C8 substrate. Methods: 20 (10 male and 10 female) healthy subjects, between 22 and 65 years of age with a BMI range of >= 18.5 and <= 29.9 kg/m2, took part in this single center open-label, randomized, two-way cross-over study. The subjects were administered linagliptin 10 mg/day and/or pioglitazone 45 mg/day until steady state was reached. Results: Co-administration of pioglitazone did not significantly affect linagliptin Cmax,ss (geometric mean ratio (GMR) 107.3; 90% confidence interval (CI); 92.3 – 124.8) or AUCTau,ss (GMR 113.4; 90% CI 103.0 – 124.9). Co-administration of linagliptin did not significantly affect pioglitazone AUCTau,ss (GMR 94.4; 90% CI 87.1 – 102.2), but reduced Cmax,ss by 14% (GMR 85.6; 90% CI 78.1 – 93.8). As expected, linagliptin and pioglitazone were well tolerated, whether administered alone or concomitantly. There were no reported serious adverse events. The investigator defined 5 adverse events as drug-related with linagliptin, and 4 with pioglitazone. Conclusions: Linagliptin and pioglitazone have no clinically relevant pharmacokinetic interaction and may be co-administered without dose adjustment. These data further confirm that linagliptin is not an inhibitor of CYP 2C8 in vivo. As the pharmacokinetic profiles of linagliptin and pioglitazone are similar in Type 2 diabetes patients and healthy subjects, it is reasonable to assume that they may be administered together to Type 2 diabetes patients without dose adjustment.
Author Details
Authors
Departments
- 1 Boehringer Ingelheim Pharma GmbH and Co. KG, Biberach/Riss, and
- 2 Boehringer Ingelheim GmbH, Ingelheim, Germany
Address
Dr. U. Graefe-Mody
Therapeutic Area Metabolism
Boehringer Ingelheim Pharma GmbH & Co. KG
Birkendorfer Str. 65, 88397 Biberach, Germany
Email:
[email protected]
Citation
E.U. Graefe-Mody, A. Jungnik, A. Ring, H.J. Woerle and K.A. Dugi.Evaluation of the pharmacokinetic interaction between the dipeptidyl peptidase-4 inhibitor linagliptin and pioglitazone in healthy volunteers. 2010; 48: 652-661. doi: 10.5414/CPP48652.
