J Clin Psychopharmacol. 2018 Jun;38(3):188-192. doi: 10.1097/JCP.0000000000000877.
Valproic acid and clozapine are drugs commonly used in the treatment of schizophrenic and schizoaffective disorders. Pharmacokinetic interactions of valproic acid with several drugs are well known, yet results concerning the interaction with clozapine are inconsistent.
Steady-state dose-corrected serum concentrations of clozapine and its main metabolite norclozapine were retrospectively analyzed in 45 patients receiving both clozapine and valproic acid. Controls were matched for sex, age, smoking, comedication, and inflammatory response.
The group receiving comedication with valproic acid showed significantly lower median dose-corrected serum concentrations of norclozapine (0.44 [0.27-0.58] (ng/mL)/(mg/d) vs 0.78 [0.60-1.07] (ng/mL)/(mg/d)) as well as metabolite to parent compound ratios (0.40 [0.36-0.47] vs 0.71 [0.58-0.84]) by approximately 44%. Dose-corrected serum concentrations of clozapine were not significantly lower. The effect of valproic acid was independent of sex and smoking.
Comedication with valproic acid accelerated metabolism of clozapine with predominant effects on the degradation of norclozapine. Therapeutic drug monitoring should be applied to guide individual patient responses upon initiation of comedication.
丙戊酸和氯氮平是常用于治疗精神分裂症和分裂情感障碍的药物。丙戊酸与几种药物的药代动力学相互作用是众所周知的，但关于与氯氮平相互作用的结果却不一致。
回顾性分析了 45 例同时服用氯氮平和丙戊酸的患者的稳态剂量校正血清氯氮平和其主要代谢物去甲氯氮平浓度。对照组按性别、年龄、吸烟、合并用药和炎症反应进行匹配。
接受丙戊酸合并用药的患者去甲氯氮平的中位数剂量校正血清浓度明显较低（0.44 [0.27-0.58]（ng/mL）/（mg/d）比 0.78 [0.60-1.07]（ng/mL）/（mg/d）），代谢物与母体化合物的比值也较低（0.40 [0.36-0.47]比 0.71 [0.58-0.84]），约为 44%。氯氮平的剂量校正血清浓度没有明显降低。丙戊酸的作用与性别和吸烟无关。
丙戊酸合并用药加速了氯氮平的代谢，主要影响去甲氯氮平的降解。在开始合并用药时，应进行治疗药物监测以指导个体患者的反应。
