Effect of esomeprazole, a proton pump inhibitor on the pharmacokinetics of sonidegib in healthy volunteers. (13th July 2016)

• Record Type: Journal Article
• Authors: Zhou, Jocelyn; Quinlan, Michelle; Glenn, Kelli; Boss, Hildegard; Picard, Franck; Castro, Henry; Sellami, Dalila
• Is Part Of: British journal of clinical pharmacology. Volume 82:Number 4(2016:Oct.)
• Page Start: 1022
• Page End: 1029
• Publication Date: 2016-07-13
• Subjects: basal cell carcinoma -- drug–drug interaction -- Hh pathway, esomeprazole -- pH‐dependent solubility -- sonidegib; Pharmacology -- Periodicals; Drugs -- Periodicals; 615.1
• DOI: 10.1111/bcp.13038
• Languages: English
• ISSNs: 0306-5251

Abstract

Abstract : 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.