Pharmacokinetic interactions between ilaprazole and clarithromycin following ilaprazole, clarithromycin and amoxicillin triple therapy

摘要

Aim:To investigate the drug interactions between ilaprazole,a new proton pump inhibitor,and clarithromycin following ilaprazole,clarithromycin and amoxicillin combination therapy.Methods:Twelve healthy Chinese volunteers were recruited in a randomized,open-label,3-period crossover study.All subjects were administered ilaprazole (5 mg),clarithromycin (500 mg) or a triple therapy,including ilaprazole (5 mg),clarithromycin (500 mg) and amoxicillin (1 g),twice daily for 6 consecutive days.On the 7th day,the drugs were given once,and blood samples were collected and analyzed using a well-validated HPLC/MS/MS method.Results:Following the triple therapy,the peak concentration (Cmax) and the area under the concentration-time curve from 0 h to 12 h (AUC0→12) of ilaprazole were significantly decreased,as compared with the single medication group (Cmax:1025.0+319.6 vs 1452.3±324.6 ng/mL; AUC0→12:9777.7±3789.8 vs 11363.1±3442.0 ng·h/mL).Similar changes were found for ilaprazole sulfone (Cmax:5.9±0.5 vs 9.3±1.7 ng/mL; AUC0→12:201.4±32.1 vs 277.1±66.2 ng.h/mL).The triple therapy significantly elevated the Cmax of clarithromycin (3161.5+702.2 vs 2541.9+476.2 ng/mL).Conclusion:The H pylori eradication therapy with clarithromycin,amoxicillin and ilaprazole may cause pharmacokinetic interactions that decrease the amount of ilaprazole and its metabolites and elevate that of clarithromycin.