Drug-drug interaction between valproic acid and meropenem: a retrospective analysis of electronic medical records from neurosurgery inpatients
Drug-drug interaction between valproic acid and meropenem: a retrospective analysis of electronic medical records from neurosurgery inpatients
复制标题
丙戊酸与美罗培南之间的药物相互作用：神经外科住院患者电子病历的回顾性分析
DOI：
10.1111/jcpt.12501
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发表时间：
2017
影响因子：
2
通讯作者：
Chen X. -P.
中科院分区：
文献类型：
--
作者：
Wen Z. -P.;Fan S. -S.;Du C.;Yin T.;Zhou B. -T.;Peng Z. -F.;Xie Y. -Y.;Zhang W.;Chen Y.;Xiao J.;Chen X. -P.
一系列研究表明，丙戊酸（VPA）与碳青霉烯类抗生素（包括美罗培南（MEPM）、亚胺培南和帕尼培南）合用时，血药浓度迅速下降，可能增加癫痫发作突破的风险。然而，VPA药代动力学变化的原因尚不清楚。方法回顾性分析2012年1月至2014年12月湘雅医院神经外科381例VPA治疗药物监测（TDM）记录。VPA TDM记录按VPA和MEPM每日剂量（g/天）分类。比较各组VPA血浆浓度，探讨药物相互作用中VPA水平的变化。结果与讨论当药物与MEPM同时使用时，VPA 1.2 g/d和1.6 g/d组的VPA血浆浓度均显着下降（67.3 ± 4.6 μg/mL，n= 21 vs15.3 ± 1.9 μg/mL，n= 15，P<0.001; 67.6 ± 1.2 μg/mL vs18.1 ± 2.6 μg/mL，n= 38，P<0.001）。在1.2 g/天VPA + MEPM、1.6 g/天VPA + MEPM和2.0 g/天VPA + MEPM组之间，未观察到VPA血药浓度存在显著差异（15.3 ± 1.9 μg/mL，n= 15 vs. 18.1 ± 2.6 μg/mL，n= 38 vs. 9.0 ± 3.0 μg/mL，n= 7;P= 0.252）。VPA浓度的降低与MEPM日剂量无关（14·0 ± 5·1μg/mL，n= 4，高MEPM日剂量vs. 16·5 ± 1·9μg/mL，n= 56，低MEPM日剂量;P= 0·729）。停用MEPM超过7天后，VPA血药浓度恢复至与开始MPEM前相当的水平（69·7 ± 4·2μg/mL，n= 21 vs. 51·2 ± 8·1μg/mL，n= 9;P= 0·48）。我们的结果表明，药物浓度的下降不能通过增加VPA剂量来逆转。此外，MEPM每日剂量不影响VPA血浆水平的下降。停用MEPM后，VPA血药浓度至少需要7天才能恢复。
What is known and objectiveA series of studies have indicated that valproic acid (VPA) plasma concentration decreased rapidly when used concomitantly with carbapenem antibiotics, including meropenem (MEPM), imipenem and panipenem, which may increase the risk of seizure breakthrough. However, the cause for the change in VPA pharmacokinetics is unclear. A retrospective analysis of VPA therapeutic drug monitoring (TDM) records was performed to investigate this VPA pharmacokinetics drug–drug interaction.MethodsThree hundred and eighty one VPA TDM records from the Department of Neurosurgery of Xiangya Hospital from January 2012 to December 2014 were collected. The VPA TDM records were categorized by VPA and MEPM daily dosages in grams/day (g/day). A comparison of VPA plasma levels among different groups was performed to investigate the change in VPA level in this drug interaction.Results and discussionRemarkable decreases in VPA plasma level were observed when the drug was used concomitantly with MEPM in both 1.2 g/d and 1.6 g/d VPA groups (67·3 ± 4·6μg/mL,n= 21 vs. 15·3 ± 1·9μg/mL,n= 15,P< 0·001; 67·6 ± 1·2μg/mL vs. 18·1 ± 2·6μg/mL,n= 38,P< 0·001). No significant difference in VPA plasma concentrations was observed between the 1·2 g/day VPA + MEPM, 1·6 g/day VPA + MEPM and 2·0 g/day VPA + MEPM groups (15·3 ± 1·9μg/mL,n= 15 vs. 18·1 ± 2·6μg/mL,n= 38 vs. 9·0 ± 3·0μg/mL,n= 7;P= 0·252). The decrease in VPA concentration was independent of MEPM daily dose (14·0 ± 5·1μg/mL,n= 4 for high MEPM daily dose vs. 16·5 ± 1·9μg/mL,n= 56 for low MEPM daily dose;P= 0·729). After discontinuation of MEPM for more than 7 days, VPA plasma concentration recovered to a value comparable to that before MPEM initiation (69·7 ± 4·2μg/mL,n= 21 vs. 51·2 ± 8·1μg/mL,n= 9;P= 0·48).What is new and conclusionThis is the first study using a large number of VPA TDM records to investigate the change in VPA levels caused by concomitant use of MEPM. Our results imply that the decrease in drug concentration cannot be reversed by increasing VPA dose. Moreover, MEPM daily dose did not influence the drop in VPA plasma level. At least 7 days are required for the recovery of VPA plasma concentration after discontinuation of MEPM.