Latour Patrick, Biraben Arnaud, Polard Elisabeth, Bentué-Ferrer Danièle, Beauplet Anne, Tribut Olivier, Allain Hervé
Department of Neurology, Hospital Cavale Blanche, Boulevard Tanguy Prigent, 29200 Brest, France.
Hum Psychopharmacol. 2004 Apr;19(3):193-203. doi: 10.1002/hup.575.
Six severe epileptic patients developed stuporous encephalopathy with marked cognitive impairment when topiramate (TPM) and sodium valproate (VPA) were coprescribed for five patients, and when monotherapy with TPM was introduced for one patient. In four patients, ammonaemia increased and then returned to normal after TPM or VPA withdrawal. This severe potential side effect must be recognized. Moreover two distinct mechanisms might explain this toxicity: (1). a pharmacokinetic interaction between VPA and TPM, leading to hyperammonaemia, (2). a pharmacodynamic mechanism due to a direct toxicity of TPM in at-risk epileptic patients.
6例重症癫痫患者在5例患者联合使用托吡酯（TPM）和丙戊酸钠（VPA）以及1例患者单独使用TPM进行单药治疗时，出现了伴有明显认知障碍的昏迷性脑病。4例患者在停用TPM或VPA后血氨升高，随后恢复正常。必须认识到这种严重的潜在副作用。此外，可能有两种不同的机制可以解释这种毒性：（1）VPA和TPM之间的药代动力学相互作用，导致高氨血症；（2）由于TPM对有风险的癫痫患者具有直接毒性作用的药效学机制。
