PMID- 27277189
OWN - NLM
STAT- MEDLINE
DCOM- 20180108
LR  - 20210109
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 82
IP  - 4
DP  - 2016 Oct
TI  - Effect of esomeprazole, a proton pump inhibitor on the pharmacokinetics of 
      sonidegib in healthy volunteers.
PG  - 1022-9
LID - 10.1111/bcp.13038 [doi]
AB  - AIMS: This study aimed to evaluate the impact of esomeprazole on the 
      pharmacokinetics of sonidegib. METHODS: This Phase I study evaluated the impact 
      of the proton pump inhibitor (PPI) esomeprazole on the oral absorption and 
      pharmacokinetics (PKs) of a single dose of sonidegib under fasted conditions. A 
      total of 42 healthy subjects were enrolled to receive either sonidegib alone 
      (200 mg single dose) or sonidegib in combination with esomeprazole (40 mg 
      pre-treatment 5 days and combination were given on day 6). Primary PK parameters 
      assessed in the study were area under the concentration-time curve (AUC) from 
      0-14 days and 0-7 days and maximum observed plasma concentration (Cmax ). 
      RESULTS: The plasma exposure (AUC0-14d, AUC0-7d and Cmax ) of a single 200 mg 
      oral dose of sonidegib was decreased by 32-38% when sonidegib was co-administered 
      with esomeprazole compared with sonidegib alone, with no apparent change in 
      elimination slope and tmax . Baseline gastric pH was similar between the two 
      arms. CONCLUSIONS: These results suggest a modest reduction in the extent of 
      sonidegib absorption by esomeprazole. There was no obvious metabolic drug-drug 
      interaction between the two agents. Both sonidegib and esomeprazole were well 
      tolerated in the study population.
CI  - (c) 2016 The British Pharmacological Society.
FAU - Zhou, Jocelyn
AU  - Zhou J
AD  - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. 
      jocelyn.zhou@novartis.com.
FAU - Quinlan, Michelle
AU  - Quinlan M
AD  - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
FAU - Glenn, Kelli
AU  - Glenn K
AD  - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
FAU - Boss, Hildegard
AU  - Boss H
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Picard, Franck
AU  - Picard F
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Castro, Henry
AU  - Castro H
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Sellami, Dalila
AU  - Sellami D
AD  - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20160713
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Proton Pump Inhibitors)
RN  - 0 (Pyridines)
RN  - 0RLU3VTK5M (sonidegib)
RN  - N3PA6559FT (Esomeprazole)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Biphenyl Compounds/adverse effects/blood/*pharmacokinetics
MH  - Drug Interactions
MH  - Esomeprazole/adverse effects/*pharmacology
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Proton Pump Inhibitors/adverse effects/*pharmacology
MH  - Pyridines/adverse effects/blood/*pharmacokinetics
MH  - Young Adult
PMC - PMC5137827
OTO - NOTNLM
OT  - Hh pathway, esomeprazole
OT  - basal cell carcinoma
OT  - drug-drug interaction
OT  - pH-dependent solubility
OT  - sonidegib
EDAT- 2016/06/10 06:00
MHDA- 2018/01/09 06:00
PMCR- 2017/10/01
CRDT- 2016/06/10 06:00
PHST- 2016/01/18 00:00 [received]
PHST- 2016/05/17 00:00 [revised]
PHST- 2016/06/04 00:00 [accepted]
PHST- 2016/06/10 06:00 [entrez]
PHST- 2016/06/10 06:00 [pubmed]
PHST- 2018/01/09 06:00 [medline]
PHST- 2017/10/01 00:00 [pmc-release]
AID - BCP13038 [pii]
AID - 10.1111/bcp.13038 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2016 Oct;82(4):1022-9. doi: 10.1111/bcp.13038. Epub 2016 Jul 
      13.