目的： 本研究探討valproate 與carbapenem 類抗生素併用時，此交互作用對valproate 藥物血中濃度及臨床實際的影響，以及不同成份的carbapenem 對valproate 血中濃度之影響程度。
方法： 以前瞻性研究探討三軍總醫院於2011 年3月1日至10 月31日，使用valproate 而其適應症為癲癇或預防癲癇發作，且併用carbapenem 類抗生素之住院病人。研究結果以平均濃度± 標準差及百分比 (%) 表示valproate 藥物血中濃度變化，並以Drug Interaction Probability Scale (DIPS) 評估二者交互作用之相關性。
結果： 本研究最後納入分析之個案數為35 名，所有患者併用carbapenem 抗生素後valproate 平均藥物濃度均有顯著降低 (p < 0.001)，其平均藥物濃度由57.9 ± 14.7 mg/L 降低至23.0 ± 17.3 mg/L，前後之藥物濃度差異為34.9 ± 20.6 mg/L，平均藥物血中濃度降低60%。併用結束後平均7 天（range 1 ~ 15 天），valproate 藥物血中濃度回昇至療效範圍。而於此段期間共有11 人 (31.4%) 癲癇再次發作。在併用期間valproate 血中濃度之平均差在doripenem、ertapenem、imipenem 及meropenem 四類藥物之間達到統計上顯著差異 (p < 0.05)，其中imipenem 對於降低valproate 血中濃度較小。
結論： Carbapenem與valproate併用時，會降低valproate血中濃度甚至導致癲癇發作。在臨床上，需避免二者併用，建議改用其它類抗生素或使用其它類的抗癲癇藥物，亦可考慮併用其它類抗癲癇藥物。
Objective: To evaluate the effect of valproate plasma concentration during co-administration of carbapenem with valproate, and the effects on clinical outcome and differences on valproate concentrations between the subclasses of carbapenem antibiotics.
Methods: A prospective study was conducted in Tri-Service General Hospital that included hospital inpatients from 1 March 2011 to 31 October 2011 who concomitantly used valproic acid with carbapenem during their hospitalisation. The valproate plasma concentration results are shown in mean ± SD and percentage forms. DIPS scores were applied to each case.
Results: A total of 35 patients met the inclusion criteria. Following the administration of carbapenem, the valproate mean plasma concentration decreased from 57.9 ± 14.8 mg/L to 23.0 ± 17.3 mg/L (p < 0.001). The mean difference in plasma valproate concentration was 34.9 ± 20.6 μg/mL,which represented an average drop of 60%. After discontinuation of carbapenem, it took 7 days for valproate concentrations to return to the therapeutic range (range 1 ~ 14 days). Eleven patients (31.4%) had acute epileptic seizures during the concomitant use of valproate and carbapenem. Kruskal-Wallis test results showed significant differences in the average decrease
in plasma VPA levels between subclasses of carbapenem antibiotics (p < 0.05). Imipenem had the least influence on valproate concentration.
Conclusions: Our study results indicate that the concomitant use of valproic acid with carbapenem results in subtherapeutic valproate plasma concentrations and corresponding increases in seizure activity.
Therefore, it would be best to avoid the concomitant use of carbapenem and valproic acid. Alternative antibiotic or anticonvulsant therapy should be considered.
