The pharmacokinetics and pharmacodynamics of alogliptin in children, adolescents, and adults with type 2 diabetes mellitus

• Published in: European journal of clinical pharmacology Vol. 73; no. 3; pp. 279 - 288
• Main Authors: Dudkowski, Caroline, Tsai, Max, Liu, Jie, Zhao, Zhen, Schmidt, Eric, Xie, Jeannie
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2017; Springer Nature B.V
• Subjects: Adolescent; Adult; Area Under Curve; Biomedical and Life Sciences; Biomedicine; Child; Clinical Trial; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Dipeptidyl-Peptidase IV Inhibitors - adverse effects; Dipeptidyl-Peptidase IV Inhibitors - pharmacokinetics; Dipeptidyl-Peptidase IV Inhibitors - pharmacology; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Female; Half-Life; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - pharmacokinetics; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Kinetics; Male; Pediatrics; Pharmacology; Pharmacology/Toxicology; Piperidines - adverse effects; Piperidines - pharmacokinetics; Piperidines - pharmacology; Piperidines - therapeutic use; Studies; Uracil - adverse effects; Uracil - analogs & derivatives; Uracil - pharmacokinetics; Uracil - pharmacology; Uracil - therapeutic use; Young Adult; Alogliptin; Pharmacodynamics; Pharmacokinetics; Pediatric patients; DPP-4 inhibition
• ISSN: 0031-6970; 1432-1041; 1432-1041
• DOI: 10.1007/s00228-016-2175-1

Purpose The aim of this study is to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of a single 12.5- or 25-mg dose of alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, in pediatric (children and adolescents) and adult subjects with type 2 diabetes mellitus (T2DM). Methods A randomized, open-label, multicenter study was conducted in pediatric and adult subjects. Subjects in two pediatric groups (children and adolescents) were randomized 1:1 to receive a single oral dose of alogliptin 12.5 or 25 mg, respectively; all gender- and race-matched adult subjects received alogliptin 25 mg. Blood and urine samples were collected at prespecified time points for PK/PD analyses. A PK/PD model was developed using data from the study for steady-state simulations. Safety was also assessed. Results In pediatric subjects receiving the 25-mg dose, the mean alogliptin peak plasma concentrations (C max ) and AUC 0-inf values were 26 and 23% lower, respectively, than in adults receiving the 25-mg dose, but maximum observed DPP-4 inhibition effect (E max ) and AUEC 0–24 values were similar to those in adults. In pediatric subjects receiving the 12.5-mg dose, the mean alogliptin C max and AUC 0-inf values were 58 and 54% lower, respectively, than those in adults, hence E max and AUEC 0–24 values were also lower by 11 and 17%, respectively. The PK/PD model simulated data were consistent with study results. No safety concern was found. Conclusions A 25-mg dose of alogliptin in pediatric subjects achieved alogliptin exposures and DPP-4 inhibition similar to those in adult T2DM patients without safety concerns; therefore, this dose is recommended for a pediatric phase 3 trial.