Factors Influencing Plasma Concentrations of Phenytoin, Phenobarbitone, Carbamazepine and Sodium Valproate in Epileptic Patients Attending a Tertiary Care Hospital

Abstract

Objective: The traditional anti-epileptic drugs like phenytoin, sodium valproate and carbamazepine continue to be used widely in the low to middle income countries due to their time tested efficacy and low costs. The factors which affect the AED concentrations in non-toxicity indications has not been reported so far. Hence, we studied the factors that could influence the plasma concentrations of these AEDs. Methods: This is a retrospective record based study and a short term prosepective study. Requisition forms of epileptic patients referred for TDM 2012-2014 were compared with the AED concentrations reported. Epileptic patients who were referred during May-June 2015 for TDM were evaluated for their seizure history and anthropometic measurements for calculation of extracellular volume (V_ECW) and compared with the AED concentrations. Results: Out of the 170 requisitions for TDM, 68.2% were monotherapy and 31.8% received two or more antiepileptic drugs. In 44% of patients, the plasma concentrations of the AED correlated with clinical response. In our study the plasma level of carbamazepine was found to be reduced by phenytoin, sodium valproate concentration was reduced by carbamazepine and phenytoin levels were reduced by sodium valproate. In male, phenytoin levels were significantly lower than in female, Phenytoin decreased carbamazepine levels significantly in female. Carbamazepine significantly decreased sodium valproate concentrations in females. Carbamazepine dose adjusted for weight and V_ECW was found to show a trend of correlation to the blood levels, Conclusion: TDM for AEDs is an indispensable investigation that guides the clinicians to tailor dose of drugs in individual patients. Factors such as age, gender, concomitant drugs in general and V_ECW in patients on carbamazepine needs to be considered while interpreting AED plasma concentrations for monitoring therapy.