Effect of esomeprazole, a proton pump inhibitor on the pharmacokinetics of sonidegib in healthy volunteers.
This study aimed to evaluate the impact of esomeprazole on the pharmacokinetics of sonidegib.



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 ).



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.



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.
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. jocelyn.zhou@novartis.com.
Jocelyn
J
Zhou
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
Michelle
M
Quinlan
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
Kelli
K
Glenn
Novartis Pharma AG, Basel, Switzerland.
Hildegard
H
Boss
Novartis Pharma AG, Basel, Switzerland.
Franck
F
Picard
Novartis Pharma AG, Basel, Switzerland.
Henry
H
Castro
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
Dalila
D
Sellami
D000293:Adolescent; D000328:Adult; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D064098:Esomeprazole / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D011725:Pyridines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
D001713:Biphenyl Compounds; D054328:Proton Pump Inhibitors; D011725:Pyridines; C561435:sonidegib; D064098:Esomeprazole
Hh pathway, esomeprazole; basal cell carcinoma; drug-drug interaction; pH-dependent solubility; sonidegib