Patsalos P N, Duncan J S
University Department of Clinical Neurology, Institute of Neurology, London, England.
Drug Saf. 1993 Sep;9(3):156-84. doi: 10.2165/00002018-199309030-00003.
Approximately 20 to 30% of patients with active intractable epilepsy are commonly treated with polytherapy antiepileptic drug regimens, and these patients may experience complicated drug interactions. Furthermore, because of the long term nature of treatment, the possibility of drug interactions with drugs used for the treatment of concomitant disease is high. Classically, clinically significant drug interactions, both pharmacokinetic and pharmacodynamic, have been considered to be detrimental to the patient, necessitating dosage adjustment. However, this need not always be the case. With the introduction of new drugs (e.g. vigabatrin and lamotrigine) with known mechanisms of action, the possibility exists that these can be used synergistically. The most commonly observed clinically significant pharmacokinetic interactions can be attributed to interactions at the metabolic and serum protein binding levels. The best known examples relate to induction (e.g. phenobarbital, phenytoin, carbamazepine and primidone) or inhibition [e.g. valproic acid (sodium valproate)] of hepatic monoxygenase enzymes. The extent and direction of interactions between the different antiepileptic drugs are varied and unpredictable. Interactions in which the metabolism of phenobarbital, phenytoin or carbamazepine is inhibited are particularly important since these are commonly associated with toxicity. Some inhibitory drugs include macrolide antibiotics, chloramphenicol, cimetidine, isoniazid and numerous sulphonamides. A reduction in efficacy of antibiotic, cardiovascular, corticosteroid, oral anticoagulant and oral contraceptive drugs occurs during combination therapy with enzyme-inducing antiepileptic drugs. Discontinuation of the enzyme inducer or inhibitor will influence the concentrations of the remaining drug(s) and may necessitate dosage readjustment.
约20%至30%的活动性难治性癫痫患者通常采用联合抗癫痫药物治疗方案，这些患者可能会经历复杂的药物相互作用。此外，由于治疗的长期性，与用于治疗伴随疾病的药物发生药物相互作用的可能性很高。传统上，具有临床意义的药代动力学和药效学药物相互作用都被认为对患者有害，需要调整剂量。然而，情况并非总是如此。随着具有已知作用机制的新药（如氨己烯酸和拉莫三嗪）的引入，存在协同使用这些药物的可能性。最常见的具有临床意义的药代动力学相互作用可归因于代谢和血清蛋白结合水平的相互作用。最著名的例子涉及肝单加氧酶的诱导（如苯巴比妥、苯妥英、卡马西平和扑米酮）或抑制作用[如丙戊酸（丙戊酸钠）]。不同抗癫痫药物之间相互作用的程度和方向各不相同且不可预测。苯巴比妥、苯妥英或卡马西平代谢受到抑制的相互作用尤为重要，因为这些通常与毒性有关。一些抑制性药物包括大环内酯类抗生素、氯霉素、西咪替丁、异烟肼和许多磺胺类药物。在与酶诱导性抗癫痫药物联合治疗期间，抗生素、心血管药物、皮质类固醇、口服抗凝剂和口服避孕药的疗效会降低。停用酶诱导剂或抑制剂会影响其余药物的浓度，可能需要重新调整剂量。
