Kim Yu C, Kang Hee E, Lee Myung G
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Biopharm Drug Dispos. 2008 Jan;29(1):51-61. doi: 10.1002/bdd.591.
It has been reported that diabetic patients have an increased risk of developing epileptic convulsions compared with the non-diabetic population, and phenytoin has widely been used for neuralgia in diabetic neuropathy. It has also been reported that in both diabetic rats induced by alloxan (DMIA rats) and by streptozotocin (DMIS rats), the protein expression and mRNA level of 2C11 decreased, but in DMIS rats, the protein expression of CYP2C6 increased. Thus, the pharmacokinetics of phenytoin and 4'-HPPH were investigated after intravenous or oral administration of phenytoin at a dose of 25 mg/kg to DMIA and DMIS rats. After intravenous or oral administration of phenytoin, the AUC (or AUC(0-12 h)) values of both phenytoin and 4'-HPPH were comparable (not significantly different) between each diabetic and the respective control rats. Although the exact reason is not clear, this could have been due to opposite protein expression (and/or mRNA levels) of CYP2C6 and 2C11 in diabetic rats.
据报道，与非糖尿病人群相比，糖尿病患者发生癫痫惊厥的风险增加，苯妥英已广泛用于治疗糖尿病性神经病变中的神经痛。也有报道称，在由四氧嘧啶诱导的糖尿病大鼠（DMIA大鼠）和由链脲佐菌素诱导的糖尿病大鼠（DMIS大鼠）中，2C11的蛋白表达和mRNA水平均降低，但在DMIS大鼠中，CYP2C6的蛋白表达增加。因此，在以25mg/kg的剂量给DMIA和DMIS大鼠静脉注射或口服苯妥英后，研究了苯妥英和4'-HPPH的药代动力学。在静脉注射或口服苯妥英后，各糖尿病大鼠与相应对照大鼠之间苯妥英和4'-HPPH的AUC（或AUC(0-12 h)）值相当（无显著差异）。尽管确切原因尚不清楚，但这可能是由于糖尿病大鼠中CYP2C6和2C11的蛋白表达（和/或mRNA水平）相反所致。
