title: The pharmacokinetics and pharmacodynamics of alogliptin in children, adolescents, and adults with type 2 diabetes mellitus.
abstract: OBJECTIVE
  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 (Cmax) and AUC0-infvalues were 26 and 23% lower, respectively, than in adults receiving the 25-mg dose, but maximum observed DPP-4 inhibition effect (Emax) and AUEC0-24values were similar to those in adults. In pediatric subjects receiving the 12.5-mg dose, the mean alogliptin Cmaxand AUC0-infvalues were 58 and 54% lower, respectively, than those in adults, hence Emaxand AUEC0-24values 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.
authors.affiliation: Takeda Development Center Americas, Inc., One Takeda Parkway, Deerfield, IL, 60015, USA. caroline.dudkowski@takeda.com.|Takeda Pharmaceuticals U.S.A., Inc., One Takeda Parkway, Deerfield, IL, 60015, USA. caroline.dudkowski@takeda.com.
authors.forename: Caroline
authors.identifier: http://orcid.org/0000-0002-5718-2533
authors.initials: C
authors.lastname: Dudkowski
authors.affiliation: Takeda Development Center Americas, Inc., One Takeda Parkway, Deerfield, IL, 60015, USA.
authors.forename: Max
authors.initials: M
authors.lastname: Tsai
authors.affiliation: Takeda Development Center Americas, Inc., One Takeda Parkway, Deerfield, IL, 60015, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Takeda Development Center Americas, Inc., One Takeda Parkway, Deerfield, IL, 60015, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Takeda Development Center Americas, Inc., One Takeda Parkway, Deerfield, IL, 60015, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Schmidt
authors.affiliation: Takeda Development Center Americas, Inc., One Takeda Parkway, Deerfield, IL, 60015, USA.
authors.forename: Jeannie
authors.initials: J
authors.lastname: Xie
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010880:Piperidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D014498:Uracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D010880:Piperidines; D014498:Uracil; C520853:alogliptin
keywords: Alogliptin; DPP-4 inhibition; Pediatric patients; Pharmacodynamics; Pharmacokinetics