伏立康唑与奥美拉唑联合应用致伏立康唑超快代谢型患者血药浓度增高的分析  

Blood Concentration of Voriconazole in Patients with Ultrarapid Metabolism Increased by Combination of Voriconazole and Omeprazole

作　　者：连玉菲[1] 刘洪涛[1] 任炳楠[1] 赵海静[1] 王彦泽 张玥[1] 田冬冬[1] 曹格溪 岳圆圆[1] 闫莉[1] LIAN Yufei;LIU Hongtao;REN Bingnan;ZHAO Haijing;WANG Yanze;ZHANG Yue;TIAN Dongdong;CAO Gexi;YUE Yuanyuan;YAN Li(Hebei General Hospital,Shijiazhuang 050051;Hebei Drug Evaluation and Certification Service Center,Shijiazhuang 050000)

机构地区：[1]河北省人民医院,河北石家庄050051 [2]河北省药品审评认证服务中心,河北石家庄050000

出　　处：《中国药物警戒》2020年第8期496-501,共6页Chinese Journal of Pharmacovigilance

基　　金：河北省医学科学研究重点课题计划(ZD20180080):临床药师依托精准医学对药物疗效及不良反应监护研究。

摘　　要：目的探讨伏立康唑与奥美拉唑钠联合应用对CYP2C19超快代谢型患者提升伏立康唑血药浓度、增强抗真菌疗效的治疗经验。方法分析总结3例伏立康唑相关基因CYP2C19超快代谢型侵袭性肺真菌病患者,依托血药浓度监测,设计并调整伏立康唑抗真菌药物治疗方案。结果 2例经临床症状、体征、痰培养提示真菌(1例为曲霉菌、1例为热带念珠菌)并结合肺CT变化,确诊为肺真菌感染的患者;第3例为化疗后IV度骨髓抑制,出现粒细胞缺乏伴发热,经规范抗感染治疗效果欠佳,需经验给予抗真菌治疗的患者。3位患者均为伏立康唑相关基因CYP2C19超快代谢型,初始给予伏立康唑抗真菌治疗效果均欠佳(临床症状无改善,血药浓度不达标),调整治疗方案增加伏立康唑单次给药剂量并联合应用奥美拉唑,抗真菌效果显著改善(伏立康唑血药谷浓度提升并达标,感染症状明显改善),成功救治患者。结论CYP2C19超快代谢型患者应用伏立康唑抗真菌治疗时,可通过奥美拉唑对伏立康唑代谢酶的竞争及抑制作用大幅增加伏立康唑血药浓度,既达到了提升伏立康唑抗真菌治疗效果的目的,又杜绝了药物调整过量所致不良反应发生的风险,为临床伏立康唑个体化治疗提供了新思路。Objective To explore the role of voriconazole combined with omeprazole sodium in increasing the blood concentration of voriconazole and enhancing antifungal efficacy in patients with CYP2 C19 ultrarapid metabolism. Methods The clinical data on three patients who had voriconazole-associated gene CYP2 C19 with ultrarapid metabolizing invasive pulmonary mycosis was analyzed. The treatment with voriconazole was designed and adjusted based on monitoring results of blood concentrations. Results Two of the three patients were diagnosed with pulmonary mycosis based on clinical symptoms, signs, and sputum culture, suggesting fungal infection(one case with Aspergillus and one case with Candida tropicalis) combined with pulmonary CT changes. The third case was a patient with degree IV myelosuppression after chemotherapy, who had agranulocytosis and fever and needed to be treated with an empirical antifungal therapy due to the poor efficacy of a standardized anti-infective therapy. All the three patients had voriconazole-associated gene CYP2 C19 with ultrarapid metabolism. The initial antifungal treatment with voriconazole was not effective(the clinical symptoms were not improved, and the blood concentration was not up to the standard). The treatment plan was adjusted by increasing the single dose of voriconazole and by combining voriconazole with omeprazole sodium so that the antifungal effect was significantly improved(the blood concentration of voriconazole increased and reached the standard, and the symptoms of infection were significantly improved), and the patients were cured. Conclusion When an antifungal therapy with voriconazole is used in patients with CYP2 C19 ultrarapid metabolism, the blood concentration of voriconazole can be greatly increased via the competition and inhibitory effect of omeprazole on voriconazole metabolism enzymes. This approach can not only improve the antifungal effect of voriconazole, but also eliminate the risk of adverse reactions caused by excessive drug adjustment. It provides a new id

关 键 词：伏立康唑 奥美拉唑钠 药物相互作用 血药浓度监测 药物代谢酶 

分 类 号：R994.11[医药卫生—毒理学]