Correlation Between Elimination Parameters of Phenytoin and Carbamazepine in Patients with Epilepsy Receiving Both Drugs Concomitantly: A Preliminary Study

Abstract

An individualized dosage regimen is of importance for phenytoin and carbamazepine therapy. However, not all patients can afford the cost of therapeutic drug monitoring, particularly in rural areas. An approach used to assist individualized drug therapy is needed. The aim of the study was to determine the relationship between maximum rate of metabolism of phenytoin and carbamazepine clearance. Such information will be beneficial in aiding individualized drug therapy. Thirteen epileptic patients receiving phenytoin in combination with carbamazepine were included in the study. All patients were studied at steady-state conditions with no change in phenytoin and carbamazepine dosage for at least one month before the study commencement. Serum phenytoin and carbamazepine concentrations were determined by Fluorescence Polarization Technique (TDx® Analyzer System). The maximum rate of metabolism of phenytoin (V max) and carbamazepine clearance (CLCBZ ) was calculated based on measured drug levels at steady-state. Subsequently, their relationships were determined by simple linear regression. There was a high correlation coefficient between maximum rate of metabolism of phenytoin (V max) and carbamazepine clearance (CLCBZ) [r = 0.816; p = 0.001 and r = 0.818; p = 0.001 for V max (mg/day) vs. CLCBZ (L/day) and V max (mg/kg/day) vs. CLCBZ (L/kg/day), respectively]. This high positive correlation can be of use in predicting V max from CLCBZ and vice versa, particularly in rural hospitals in Thailand where therapeutic drug monitoring for either one of the drugs is not available. Elimination parameters of phenytoin and carbamazepine can be predicted by their respective relationships. The proposed equations used to determine maximum rate of metabolism of phenytoin and carbamazepine clearance are of benefit in reducing the cost for drug concentration measurements.