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.
RCT Entities:
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.
Authors: N R Budha; A Frymoyer; G S Smelick; J Y Jin; M R Yago; M J Dresser; S N Holden; L Z Benet; J A Ware Journal: Clin Pharmacol Ther Date: 2012-06-27 Impact factor: 6.875
Authors: Michael R Migden; Alexander Guminski; Ralf Gutzmer; Luc Dirix; Karl D Lewis; Patrick Combemale; Robert M Herd; Ragini Kudchadkar; Uwe Trefzer; Sven Gogov; Celine Pallaud; Tingting Yi; Manisha Mone; Martin Kaatz; Carmen Loquai; Alexander J Stratigos; Hans-Joachim Schulze; Ruth Plummer; Anne Lynn S Chang; Frank Cornélis; John T Lear; Dalila Sellami; Reinhard Dummer Journal: Lancet Oncol Date: 2015-05-14 Impact factor: 41.316
Authors: H P Parkman; J L Urbain; L C Knight; K L Brown; D M Trate; M A Miller; A H Maurer; R S Fisher Journal: Gut Date: 1998-02 Impact factor: 23.059
Authors: J E Richter; P J Kahrilas; J Johanson; P Maton; J R Breiter; C Hwang; V Marino; B Hamelin; J G Levine Journal: Am J Gastroenterol Date: 2001-03 Impact factor: 10.864