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

作　　者：Shan CAO Gan ZHOU Dong-sheng OU-YANG Hui-zi WU Kui XIAO Yao CHEN Dong GUO Lan FAN Zhi-rong TAN Hai-tang HU Xiang-hong QIN Hong-hao ZHOU Wei ZHANG 

机构地区：[1]Institute of Clinical Pharmacology,Hunan Key Laboratory of Pharmacogenetics,Central South University,Changsha 410078,China [2]Department of Respiratory Medicine,The Second Xiangya Hospital,Central South University,Changsha 410011,China

出　　处：《Acta Pharmacologica Sinica》2012年第8期1095-1100,共6页中国药理学报（英文版）

基　　金：We would like to thank Mary W ROEDERER, PharmD, BCPS, at the UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA, for her contribution to the preparation of this manu-script. This work was supported by the National Natural Science Foundation of China （No 30801421, 30901834, and 30873089）, the Huge Project to Boost Chinese Drug Development, （No 2009ZX09501-032）, the 863 Project （No 2009AA022710, 2009AA022703, and 2009AA022704）, the New Century Excellent Talents Project （NCET-10-0843） and Funda-mental Research Funds for the Central Universities （No 2010QZZD010）.

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.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.

关 键 词：peptic ulcer Helicobacter pylori infection eradication therapy CLARITHROMYCIN AMOXICILLIN ilaprazole PHARMACOKINETICS druginteraction 

分 类 号：TQ465.5[化学工程—制药化工] O562.5[理学—原子与分子物理]