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Effect of esomeprazole, a proton pump inhibitor on the pharmacokinetics of sonidegib in healthy volunteers
Author(s) -
Zhou Jocelyn,
Quinlan Michelle,
Glenn Kelli,
Boss Hildegard,
Picard Franck,
Castro Henry,
Sellami Dalila
Publication year - 2016
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13038
Subject(s) - esomeprazole , pharmacokinetics , medicine , proton pump inhibitor , pharmacology , drug interaction , urology , gastroenterology
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 ( C max ). Results The plasma exposure (AUC0 ‐ 14d, AUC0 ‐ 7d and C max ) 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 t max . 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.