PMID- 27128836
OWN - NLM
STAT- MEDLINE
DCOM- 20180116
LR  - 20180705
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Linking)
VI  - 3
IP  - 4
DP  - 2014 Jul
TI  - Population pharmacokinetic analysis of dutogliptin, a selective dipeptidyl 
      peptidase-4 inhibitor.
PG  - 297-304
LID - 10.1002/cpdd.87 [doi]
AB  - Dutogliptin is a selective dipeptidyl peptidase-4 inhibitor shown to be 
      efficacious and safe in patients with type 2 diabetes mellitus (T2DM). Population 
      pharmacokinetic (PK) analysis of dutogliptin was performed based on data 
      collected in 561 healthy subjects and patients with T2DM enrolled in Phase I and 
      II studies to assess sources of variability and support dosing rationale. The 
      effect of extrinsic (formulations, fed/fasting conditions, potential drug-drug 
      interaction with metformin) and intrinsic (baseline characteristics, markers of 
      renal function, renal impairment category, and disease status) covariates was 
      evaluated using non-linear mixed effect modeling. Plasma concentrations of 
      dutogliptin were best fitted with a two-compartment model with a first-order rate 
      constant of absorption (Ka) and a lag time. No differences were observed between 
      healthy subjects and patients with T2DM. Apparent clearance (CL/F) and terminal 
      elimination half-life of dutogliptin were 176 L/h and 12.2 hours, respectively. 
      Typical CL/F values in patients with mild and moderate renal impairment were 121 
      and 79 L/h, respectively. No drug-drug interaction was observed with metformin. 
      These results suggest that a reduction in dosing from 400 to 200 mg daily is 
      warranted in T2DM patients with moderate renal impairment. No dose adjustments 
      were deemed necessary for other evaluated patient characteristics and 
      coadministration with metformin.
CI  - (c) 2014, The American College of Clinical Pharmacology.
FAU - Marier, Jean-Francois
AU  - Marier JF
AD  - Pharsight, A Certara Company, Montreal, QC, Canada.
FAU - Mouksassi, Mohamad-Samer
AU  - Mouksassi MS
AD  - Pharsight, A Certara Company, Montreal, QC, Canada.
FAU - Gosselin, Nathalie H
AU  - Gosselin NH
AD  - Pharsight, A Certara Company, Montreal, QC, Canada.
FAU - Li, Jianke
AU  - Li J
AD  - Phenomix Corporation, San Diego, CA, USA.
AD  - Ambit Biosciences Corporation, San Diego, CA, USA.
LA  - eng
PT  - Journal Article
DEP - 20140210
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Boronic Acids)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 38EAO245ZX (dutogliptin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Boronic Acids/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Clinical Trials, Phase I as Topic
MH  - Clinical Trials, Phase II as Topic
MH  - Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy
MH  - Dipeptidyl-Peptidase IV Inhibitors/administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Drug Monitoring
MH  - Female
MH  - Half-Life
MH  - Humans
MH  - Kidney/physiopathology
MH  - Kidney Diseases/diagnosis/physiopathology
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Middle Aged
MH  - *Models, Biological
MH  - Nonlinear Dynamics
MH  - Risk Factors
MH  - Young Adult
OTO - NOTNLM
OT  - DPP-4 inhibitor
OT  - dutogliptin
OT  - pharmacokinetics
OT  - sources of variability
EDAT- 2014/07/01 00:00
MHDA- 2014/07/01 00:01
CRDT- 2016/04/30 06:00
PHST- 2013/04/09 00:00 [received]
PHST- 2013/10/15 00:00 [accepted]
PHST- 2016/04/30 06:00 [entrez]
PHST- 2014/07/01 00:00 [pubmed]
PHST- 2014/07/01 00:01 [medline]
AID - 10.1002/cpdd.87 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2014 Jul;3(4):297-304. doi: 10.1002/cpdd.87. Epub 2014 
      Feb 10.