PMID- 24504700
OWN - NLM
STAT- MEDLINE
DCOM- 20160531
LR  - 20220408
IS  - 2107-0180 (Electronic)
IS  - 0378-7966 (Print)
IS  - 0378-7966 (Linking)
VI  - 39
IP  - 3
DP  - 2014 Sep
TI  - The pharmacokinetics of conventional and bioenhanced tablet formulations of 
      danirixin (GSK1325756) following oral administration in healthy, elderly, human 
      volunteers.
PG  - 173-81
LID - 10.1007/s13318-014-0179-8 [doi]
AB  - Danirixin (GSK1325756) is a small, high-affinity, selective and reversible CXCR2 
      antagonist in development for treatment of chronic obstructive pulmonary disease. 
      The objective of the study was to evaluate the relative bioavailability, 
      including the inter-subject variability, of a conventional immediate-release (IR) 
      formulation and two prototype bioenhanced formulations of danirixin during 
      gastric acid suppression in a healthy, elderly population. A single-centre, 
      crossover study in healthy male and female volunteers aged 65-80 years was 
      conducted. Subjects were randomised to receive danirixin 50 mg IR in the fed and 
      fasted states and danirixin 50 mg Bioenhanced Formulation 1 and 2 in the fasted 
      state. All subjects also received omeprazole 20 mg each morning beginning 4 days 
      prior to the first treatment period and continuing through danirixin dosing in 
      the final treatment period. Twenty subjects were randomised and completed the 
      study. Bioenhanced Formulation 2 in the fasted state demonstrated the highest 
      adjusted geometric means for AUC(0-t), AUC(0-inf), AUC(0-24) and C max. Danirixin 
      IR demonstrated adjusted means that were higher in the fed state compared with 
      the fasted state. For all formulations tested, there was substantial 
      inter-subject variability (CVb >100 % for all formulations). The overall 
      incidences of adverse events (AEs) were 10 % for danirixin IR (both in the fed 
      and fasted states) and 15-20 % for the bioenhanced formulations. The majority of 
      AEs were mild in intensity. There were no serious AEs. Concomitant use of 
      omeprazole resulted in large inter-subject variability in the exposure to 
      danirixin. Bioenhanced formulation strategies could not overcome the effect of 
      omeprazole on exposure and variability between subjects.
FAU - Miller, Bruce E
AU  - Miller BE
AD  - Clinical Discovery, Respiratory Therapy Area Unit, GlaxoSmithKline R&D, 709 
      Swedeland Road, King of Prussia, PA, 19406, USA, bruce.e.miller@gsk.com.
FAU - Smart, Kevin
AU  - Smart K
FAU - Mistry, Sunil
AU  - Mistry S
FAU - Ambery, Claire L
AU  - Ambery CL
FAU - Bloomer, Jackie C
AU  - Bloomer JC
FAU - Connolly, Paul
AU  - Connolly P
FAU - Sanderson, Dominic
AU  - Sanderson D
FAU - Shreeves, Trevor
AU  - Shreeves T
FAU - Smith, Rachel
AU  - Smith R
FAU - Lazaar, Aili L
AU  - Lazaar AL
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140207
PL  - France
TA  - Eur J Drug Metab Pharmacokinet
JT  - European journal of drug metabolism and pharmacokinetics
JID - 7608491
RN  - 0 (Piperidines)
RN  - 0 (Proton Pump Inhibitors)
RN  - 0 (Respiratory System Agents)
RN  - 0 (Sulfones)
RN  - 0 (Tablets)
RN  - KG60484QX9 (Omeprazole)
RN  - R318PGH5VP (danirixin)
SB  - IM
MH  - Administration, Oral
MH  - Age Factors
MH  - Aged
MH  - Biological Availability
MH  - Chemistry, Pharmaceutical
MH  - Cross-Over Studies
MH  - Drug Interactions
MH  - England
MH  - Fasting/blood
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Male
MH  - Omeprazole/administration & dosage
MH  - Piperidines/*administration & dosage/adverse 
      effects/blood/chemistry/*pharmacokinetics
MH  - Postprandial Period
MH  - Proton Pump Inhibitors/administration & dosage
MH  - Respiratory System Agents/*administration & dosage/adverse 
      effects/blood/chemistry/*pharmacokinetics
MH  - Solubility
MH  - Sulfones/*administration & dosage/adverse 
      effects/blood/chemistry/*pharmacokinetics
MH  - Tablets
PMC - PMC4142138
EDAT- 2014/02/08 06:00
MHDA- 2016/06/01 06:00
PMCR- 2014/02/07
CRDT- 2014/02/08 06:00
PHST- 2013/06/18 00:00 [received]
PHST- 2014/01/22 00:00 [accepted]
PHST- 2014/02/08 06:00 [entrez]
PHST- 2014/02/08 06:00 [pubmed]
PHST- 2016/06/01 06:00 [medline]
PHST- 2014/02/07 00:00 [pmc-release]
AID - 179 [pii]
AID - 10.1007/s13318-014-0179-8 [doi]
PST - ppublish
SO  - Eur J Drug Metab Pharmacokinet. 2014 Sep;39(3):173-81. doi: 
      10.1007/s13318-014-0179-8. Epub 2014 Feb 7.