The relationship between pharmacokinetic parameters of phenytoin and carbamazepine in epileptic patients

Abstract

Objective: Phenytoin (PHT) and carbamazepine (CBZ) are commonly prescribed together for treatment of epilepsy in patients who cannot control seizures with single drug. Both drugs are mainly metabolized via cytochrome P450, it is therefore possible that their pharmacokinetic parameters would be related. This study was designed to determine the correlation between pharmacokinetic parameters of the two drugs and provide regression equations to predict pharmacokinetic parameters of PHT from CBZ, and vice versa. Moreover, this study was also designed to compare the maximum rate of metabolism of phenytoin (Vmax) and carbamazepine clearance (ClCBZ) when used as a monotherapy with those obtained from incombination therapy. Method: A retro-prospective observational pharmacokinetic design was performed in 48 epileptic patients. They were categorized into 3 groups: PHT-CBZ combination therapy group, PHT monotherapy group and CBZ monotherapy group. One blood sample was collected from each patient at steady state condition. Serum drug concentrations of both drugs were determined. Vmax and ClCBZ were calculated, correlation coefficients and regression equation were performed. Comparisons of Vmax and ClCBZ between monotherapy group and combination therapy group were also determined to evaluate the pharmacokinetic interaction between two drugs. Results: There was a significant linear correlation between Vmax and ClCBZ (r=0.828; P = 0.001). Vmax between monotherapy group and combination therapy group were not significantly different (362.80 ± 51.78 and 331.64 ± 71.93; P = 0.170) while ClCBZ were significantly different (105.35 ± 35.45 and 76.45 ± 26.62; P = 0.014) between monotherapy group and combination therapy group. Conclusion: Vmax could be accurately predicted from ClCBZ and vice versa. This would save cost for patients.