Regional Health Agency of Tuscany, Firenze, Italy.
Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy.
Epileptic Disord. 2021 Apr 1;23(2):229-256. doi: 10.1684/epd.2021.1261.
Comorbidity between epilepsy and infectious diseases in children is frequent. Pharmacokinetic drug-drug interactions (DDIs) between antiseizure medications (ASMs) and anti-infectives can occur and influence their efficacy or cause toxicity. All potential DDIs between ASMs and antimicrobial agents used in children were identified through consultation of drug compendia. Clinical studies, case reports and summaries of product characteristics of all identified drugs were also searched. A typical example of a DDI that is often observed in children is that involving valproate (VPA) and carbapenem antibiotics. This DDI has a unique mechanism of action (inhibits the enzyme that catalyses the hydrolysis of VPA-glucuronide) and leads to a fall of around 60% of VPA level, associated with seizure recurrence. An example of bidirectional DDI involves the antimycotic voriconzole and several ASMs. Voriconazole is metabolized and is a strong inhibitor of cytochrome (CYP)3A4, CYP2C9/10 and CYP2C19. There is clinical evidence of induction of voriconazole metabolism with possible loss of its efficacy by phenytoin (PHT), while voriconazole increases the levels of PHT. Other ASMs that are inducers of these enzymes, such as carbamazepine (CBZ), phenobarbital, stiripentol and to a lesser degree, oxcarbazepine, might be predicted to decrease the level of voriconazole. Voriconazole might also be predicted to increase levels of cannabidiol, CBZ, lacosamide, midazolam, and zonisamide. DDIs between ASMs and some antiviral agents are potentially even more frequent and clinically relevant.
儿童癫痫与感染性疾病共存的情况较为常见。抗癫痫药物（ASM）与抗感染药物之间可能发生药代动力学药物-药物相互作用（DDI），从而影响其疗效或导致毒性。通过查阅药物学手册，确定了所有可能存在于 ASM 与儿童用抗菌药物之间的潜在 DDI。还对所有确定药物的临床研究、病例报告和产品特性摘要进行了检索。在儿童中经常观察到的一种 DDI 是涉及丙戊酸（VPA）和碳青霉烯类抗生素的 DDI。这种 DDI 具有独特的作用机制（抑制催化 VPA-葡萄糖醛酸水解的酶），导致 VPA 水平下降约 60%，与癫痫发作复发有关。一个双向 DDI 的例子涉及抗真菌药伏立康唑和几种 ASM。伏立康唑被代谢，并强烈抑制细胞色素（CYP）3A4、CYP2C9/10 和 CYP2C19。有临床证据表明伏立康唑的代谢被苯妥英（PHT）诱导，可能使其疗效丧失，而伏立康唑则增加 PHT 的水平。其他诱导这些酶的 ASM，如卡马西平（CBZ）、苯巴比妥、司替戊醇，以及在较小程度上的奥卡西平，可能被预测会降低伏立康唑的水平。伏立康唑也可能被预测会增加大麻二酚、CBZ、拉科酰胺、咪达唑仑和左乙拉西坦的水平。ASM 与一些抗病毒药物之间的 DDI 可能更频繁且具有临床相关性。
