Spina Edoardo, Perucca Emilio
Institute of Pharmacology, University of Messina, Messina, Italy.
Epilepsia. 2002;43 Suppl 2:37-44. doi: 10.1046/j.1528-1157.2002.043s2037.x.
As antiepileptic drugs (AEDs) and psychotropic agents are increasingly used in combination, the possibility of pharmacokinetic interactions between these compounds is relatively common. Most pharmacokinetic interactions between AEDs and psychoactive drugs occur at a metabolic level, and usually involve changes in the activity of the cytochrome P450 mixed-function oxidases (CYP) involved in their biotransformation. As a consequence of CYP inhibition or induction, plasma concentrations of a given drug may reach toxic or subtherapeutic levels, and dosage adjustments may be required to avoid adverse effects or clinical failure. Enzyme-inducing AEDs, such as carbamazepine (CBZ), phenytoin (PHT), and barbiturates, stimulate the oxidative biotransformation of many concurrently prescribed psychotropics. In particular, these AEDs may decrease the plasma concentrations of tricyclic antidepressants, many antipsychotics, including traditional compounds, i.e., haloperidol and chlorpromazine, and newer agents, i.e., clozapine, risperidone, olanzapine, quetiapine, and ziprasidone, and some benzodiazepines. Conversely, new AEDs appear to have a lower potential for interactions with all psychotropic drugs. While antipsychotics and anxiolytics do not significantly influence the pharmacokinetics of most AEDs, some newer antidepressants, such as viloxazine, fluoxetine, and fluvoxamine, may lead to higher serum levels of some AEDs, namely CBZ and PHT, through inhibition of CYP enzymes. No significant pharmacokinetic interactions have been documented between AEDs and lithium. Information about CYP enzymes responsible for the biotransformation of individual agents and about the effects of these compounds on the activity of specific CYP enzymes may help in predicting and avoiding clinically significant interactions. Apart from careful clinical observation, serum level monitoring of AEDs and psychotropic drugs can be useful in determining the need for dosage adjustments, especially if there is any change in seizure control, or possible toxicity.
随着抗癫痫药物（AEDs）与精神药物联合使用的情况日益增多，这些化合物之间发生药代动力学相互作用的可能性相对常见。AEDs与精神活性药物之间的大多数药代动力学相互作用发生在代谢水平，通常涉及参与其生物转化的细胞色素P450混合功能氧化酶（CYP）活性的变化。由于CYP抑制或诱导作用，特定药物的血浆浓度可能达到中毒或低于治疗水平，可能需要调整剂量以避免不良反应或临床治疗失败。酶诱导性AEDs，如卡马西平（CBZ）、苯妥英（PHT）和巴比妥类药物，会刺激许多同时开具的精神药物的氧化生物转化。特别是，这些AEDs可能会降低三环类抗抑郁药、许多抗精神病药物（包括传统化合物，如氟哌啶醇和氯丙嗪，以及新型药物，如氯氮平、利培酮、奥氮平、喹硫平和齐拉西酮）以及一些苯二氮䓬类药物的血浆浓度。相反，新型AEDs与所有精神药物发生相互作用的可能性似乎较低。虽然抗精神病药物和抗焦虑药物对大多数AEDs的药代动力学没有显著影响，但一些新型抗抑郁药，如维洛沙嗪、氟西汀和氟伏沙明，可能通过抑制CYP酶导致某些AEDs（即CBZ和PHT）的血清水平升高。尚未有AEDs与锂之间发生显著药代动力学相互作用的记录。有关负责个体药物生物转化的CYP酶以及这些化合物对特定CYP酶活性影响的信息，可能有助于预测和避免具有临床意义的相互作用。除了仔细的临床观察外，监测AEDs和精神药物的血清水平有助于确定是否需要调整剂量，特别是在癫痫控制出现任何变化或可能存在毒性的情况下。
