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表皮生长因子受体多态性对酪氨酸激酶抑制剂药效学影响的研究进展

ISSN号：1009-2501
期刊名称：《中国临床药理学与治疗学》
时间：0
分类：TQ465.5[化学工程—制药化工] O562.5[理学—原子与分子物理;理学—物理]
作者机构：[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
相关基金：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）.

关键词：动力学相互作用, 克拉霉素, 阿莫西林, 药代动力学, 疗法, 三联, 质子泵抑制剂, 幽门螺旋杆菌, peptic ulcer, Helicobacter pylori infection, eradication therapy, clarithromycin, amoxicillin, ilaprazole, pharmacokinetics, druginteraction

中文摘要：

瞄准: 调查在 ilaprazole，一个新质子泵禁止者，和 clarithromycin 追随者 ilaprazole 之间的药相互作用， clarithromycin 和 amoxicillin 联合治疗。

英文摘要：

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.

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