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

被引:15
作者
Dudkowski, Caroline [1 ,2 ]
Tsai, Max [1 ]
Liu, Jie [1 ]
Zhao, Zhen [1 ]
Schmidt, Eric [1 ]
Xie, Jeannie [1 ]
机构
[1] Takeda Dev Ctr Amer Inc, One Takeda Pkwy, Deerfield, IL 60015 USA
[2] Takeda Pharmaceut USA Inc, One Takeda Pkwy, Deerfield, IL 60015 USA
关键词
Alogliptin; Pharmacokinetics; Pharmacodynamics; Pediatric patients; DPP-4; inhibition; PEPTIDASE-4 INHIBITOR ALOGLIPTIN; INADEQUATE GLYCEMIC CONTROL; DOUBLE-BLIND; DIPEPTIDYL PEPTIDASE-4; PIOGLITAZONE; METFORMIN; EFFICACY; SAFETY; TOLERABILITY; COMBINATION;
D O I
10.1007/s00228-016-2175-1
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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). 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. 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. 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.
引用
收藏
页码:279 / 288
页数:10
相关论文
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