ORIGINAL RESEARCH ARTICLE Comparable Liraglutide Pharmacokinetics in Pediatric and Adult Populations with Type 2 Diabetes: A Population Pharmacokinetic Analysis

The Author(s) 2015. This article is published with open access at Springerlink.com Background and Objective The safety, tolerability, and pharmacokinetics of the once-daily human glucagon-like peptide-1 (GLP-1) analog liraglutide have been evaluated in pediatric patients aged greater than 10 years with type 2 diabetes (T2D). In this study, a population pharmacokinetic analysis was compared to the pediatric pharmacokinetic data with those from two clinical pharmacology trials in adults with T2D. Methods A one-compartment pharmacokinetic model previously found to adequately describe the pharmacoki-netics of liraglutide in adults with T2D was applied to the evaluation of 13 pediatric subjects (10–17 years of age) with T2D. Steady-state estimates for apparent clearance (CL/F) for individual subjects and corresponding dose were used to derive the area under the plasma–concentration time curve from 0–24 h (AUC24) and investigate dose proportionality in the pediatric trial. A covariate analysis evaluated the effects of body weight, gender, and age category (pediatric/adult) on liraglutide exposure. Results Dose proportionality in the dose range of 0.3–1.8 mg was indicated by the model-derived AUC24 slope: 1.05 (95 % CI 0.96–1.15). Consistent with findings from adult trials, body weight and gender were relevant covariates for liraglutide exposure in the pediatric popu-lation. The CL/F estimates, and thus exposure, for the pediatric subjects with T2D were similar to those in the adult trials. Conclusion Based on this population pharmacokinetic analysis, the liraglutide dose regimen that was found to be clinically effective in adults is predicted to achieve the same range of exposure in the pediatric population (10–17 years of age) with a pre-trial body weight range of 57–214 kg. Key Points This model predicts that the liraglutide dose regimen used in adults will result in the same range of exposures in the pediatric population (10–17 years) with type 2 diabetes (T2D). This pharmacokinetic analysis of liraglutide in pediatric subjects with T2D could help broaden the range of treatment options for this population.