Gidal B E, Zupanc M L
Center for Health Sciences (CHS), School of Pharmacy, University of Wisconsin, Madison 53706.
Ann Pharmacother. 1994 Apr;28(4):455-8. doi: 10.1177/106002809402800405.
To report a case of a potential pharmacokinetic interaction between felbamate and phenobarbital in a patient with epilepsy.
A patient with a history of a mixed seizure disorder and static encephalopathy who was receiving sodium valproate 750 mg/d and phenobarbital 230 mg/d was initiated on felbamate (as part of a compassionate use program). Upon instituting felbamate, valproate dosage was reduced to 500 mg/d and phenobarbital to 200 mg/d. Felbamate dosage was titrated to approximately 50 mg/kg/d over three weeks. In this patient, plasma phenobarbital concentrations increased from 48 micrograms/mL to 68 micrograms/mL, at which point the patient was hospitalized because of clinically significant neurotoxicity. Phenobarbital dosage was subsequently reduced to 150 mg/d; this resulted in phenobarbital trough concentrations of 60 micrograms/mL.
Felbamate has been shown previously to interact with multiple other anticonvulsant medications, including valproate, phenytoin, and carbamazepine. Felbamate appears to decrease the clearance of valproate, phenytoin, and carbamazepine epoxide to a significant extent, an effect that may be the result of inhibition of the metabolism of these compounds. Carbamazepine plasma concentrations have been demonstrated to decrease following administration of felbamate, suggesting metabolic induction. It is reasonable to suggest that based on these findings and the observations in our patient, felbamate comedication may result in clinically significant increases in plasma phenobarbital concentrations. It would seem prudent, therefore, when initiating or adjusting felbamate therapy in patients receiving this drug combination, to monitor phenobarbital plasma concentrations.
报告1例癫痫患者中 felbamate 与苯巴比妥之间可能存在的药代动力学相互作用。
1例有混合性癫痫发作障碍和静止性脑病病史的患者，正在接受丙戊酸钠750 mg/d和苯巴比妥230 mg/d治疗，开始使用 felbamate（作为一项同情用药计划的一部分）。开始使用 felbamate 后，丙戊酸钠剂量减至500 mg/d，苯巴比妥减至200 mg/d。在3周内将 felbamate 剂量滴定至约50 mg/kg/d。该患者血浆苯巴比妥浓度从48微克/毫升升至68微克/毫升，此时患者因具有临床意义的神经毒性而住院。随后苯巴比妥剂量减至150 mg/d；这导致苯巴比妥谷浓度为60微克/毫升。
先前已表明 felbamate 可与多种其他抗惊厥药物相互作用，包括丙戊酸盐、苯妥英和卡马西平。Felbamate 似乎在很大程度上降低了丙戊酸盐、苯妥英和卡马西平环氧化物的清除率，这种作用可能是这些化合物代谢受到抑制的结果。已证明服用 felbamate 后卡马西平血浆浓度降低，提示代谢诱导。根据这些发现以及我们患者中的观察结果，合理推测 felbamate 联合用药可能导致血浆苯巴比妥浓度出现具有临床意义的升高。因此，在接受这种药物组合的患者中开始或调整 felbamate 治疗时，监测苯巴比妥血浆浓度似乎是谨慎的做法。
