Liu H, Delgado M R
Department of Research, Texas Scottish Rite Hospital for Children, University of Texas Southwestern Medical Center, Dallas 75219.
Epilepsy Res. 1994 Mar;17(3):257-69. doi: 10.1016/0920-1211(94)90056-6.
The influence of polytherapy on the relationships between the age, weight, carbamazepine (CBZ) dose, total clearance, and intrinsic clearance, with concentrations, concentration ratios, and level/dose ratios of CBZ, carbamazepine-10,11-epoxide (CBZ-E) and trans-10,11-dihydroxy-10,11-dihydro-carbamazepine (CBZ-H) are investigated. Three groups of patients with CBZ monotherapy, or receiving CBZ polytherapy by taking CBZ and valproic acid (VPA) or CBZ plus other antiepileptic drugs (AEDs) were studied. The significant correlations between serum CBZ concentrations and CBZ dose in patients taking CBZ alone were no longer significant in patients with polytherapy, and the positive associations between serum CBZ-E concentrations and CBZ dose were lost in patients with CBZ + VPA. Only the concentrations of CBZ-H had significant correlations with CBZ dose in all three groups of patients. Results from this relationship study indicate a heteroinduction effect of other AEDs on CBZ metabolism, and a relatively weak influence on CBZ-E elimination. Data also suggest that there is a block in the biotransformation from CBZ-E to CBZ-H in patients taking CBZ + VPA, presumably caused by the inhibition effect of VPA on epoxide hydrolase. Therapeutic drug monitoring of CBZ will benefit from the knowledge obtained from the relationship study.
研究了联合治疗对年龄、体重、卡马西平（CBZ）剂量、总清除率和内在清除率与CBZ、卡马西平-10,11-环氧化物（CBZ-E）和反式-10,11-二羟基-10,11-二氢卡马西平（CBZ-H）的浓度、浓度比及血药浓度/剂量比之间关系的影响。研究了三组患者，分别为接受CBZ单药治疗的患者，或通过服用CBZ与丙戊酸（VPA）联合治疗的患者，以及服用CBZ加其他抗癫痫药物（AEDs）联合治疗的患者。单独服用CBZ的患者中，血清CBZ浓度与CBZ剂量之间的显著相关性在联合治疗的患者中不再显著，且在CBZ + VPA治疗的患者中，血清CBZ-E浓度与CBZ剂量之间的正相关关系消失。在所有三组患者中，只有CBZ-H的浓度与CBZ剂量存在显著相关性。该相关性研究结果表明，其他AEDs对CBZ代谢具有异源诱导作用，对CBZ-E消除的影响相对较弱。数据还表明，服用CBZ + VPA的患者中存在从CBZ-E到CBZ-H生物转化的阻滞，推测这是由VPA对环氧水解酶的抑制作用所致。CBZ的治疗药物监测将受益于从该相关性研究中获得的知识。
