碳青霉烯类抗菌药物与丙戊酸存在临床意义的药物相互作用

Interaction between valproic acid and carbapenem antibiotics

目的以临床发现的美罗培南显著降低丙戊酸(VPA)的血药浓度为线索,探讨碳青霉烯类药物与丙戊酸之间的相互作用问题。方法检索中文CNKI和万方数据库和Pubmed数据库,获取已经报道了关于碳青霉烯类药物对丙戊酸血药浓度的影响及其机制研究。结果中文CNKI收录的文献中无相关报道;而Pubmed数据库中共发现35例碳青霉烯类抗菌药物和丙戊酸合用,导致游离丙戊酸血药浓度显著降低,甚至诱发癫痫发作的报道;体内和体外的相互作用机制研究显示,合用碳青霉烯类药物影响了VPA的吸收、分布和代谢:抑制丙戊酸的吸收;增加血浆中丙戊酸向红细胞的转运;抑制葡萄糖醛酸结合的丙戊酸(VPAG)解离为游离的丙戊酸,后者是美罗培南和丙戊酸相互作用的主要机制。结论临床应该避免合用碳青霉烯类药物和丙戊酸,两者之间的不良药物相互作用不能通过调整丙戊酸的剂量而减轻,临床必须应用碳青霉烯类药物时可选择苯妥英钠或卡马西平等抗癫痫药物。

OBJECTIVE To discuss the drug interaction between carbapenem antibiotics and valprate based on the clinical finding that concurrently use of meropenem could significantly decrease the serum concentration of valproic acid.METHODS Researches about the interaction between carbapenen antibiotics and valproic acid or related case reports were indexed from the China CNKI and/ or wanfang data and the Pubmed data base.RESULTS No related study or case report was included in the China database.35 case reports about the combination use of carbapenem antibiotics with valproic acid,which could cause remarkable decrease of plasma concentration of free valproic acid and even could induce epilepsy,were searched from the Pubmed database.It was confirmed that carbpenem antibiotics interfered the absorption,distribution and metabolism of valproic acid,inhibiting the absorption of valproic acid,increasing erythrocyte distribution from plasma;and suppressing the valproic acid glucuronide hydrolase and reducing serum free valproic acid.CONCLUSION Concurrently use of carbpenem antibiotics and valproic acid should be avoided and this adverse drug interaction outcome can not be relieved by adjusting valproic acid oral dose.If it is necessary to use carbpenem antibiotics,other AEDs such as phentoin sodium or carbamazepine should be considered.