共 21 条
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.
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页码:279 / 288
页数:10
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