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

作者：Cao, Shan; Zhou, Gan; Ou-Yang, Dong-sheng; Wu, Hui-zi; Xiao, Kui; Chen, Yao; Guo, Dong; Fan, Lan; Tan, Zhi-rong; Hu, Hai-tang; Qin, Xiang-hong; Zhou, Hong-hao; Zhang, Wei^*

来源：Acta Pharmacologica Sinica, 2012, 33(8): 1095-1100.

DOI：10.1038/aps.2012.64

• peptic ulcer
• Helicobacter pylori infection
• eradication therapy
• clarithromycin
• amoxicillin
• ilaprazole
• pharmacokinetics
• drug interaction

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 (C-max) and the area under the concentration-time curve from 0 h to 12 h (AUC(0 -> 12)) of ilaprazole were significantly decreased, as compared with the single medication group (C-max: 1025.0 +/- 319.6 vs 1452.3 +/- 324.6 ng/mL; AUC(0 -> 12): 9777.7 +/- 3789.8 vs 11363.1 +/- 3442.0 ng.h/mL). Similar changes were found for ilaprazole sulfone (C-max: 5.9 +/- 0.5 vs 9.3 +/- 1.7 ng/mL; AUC(0 -> 12): 201.4 +/- 32.1 vs 277.1 +/- 66.2 ng.h/mL). The triple therapy significantly elevated the C-max 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.

• 出版日期2012-8
• 单位中南大学