Analysis of phenytoin drug concentration for evaluation of clinical response, uncontrolled seizures and toxicity

ABSTRACT

The narrow therapeutic index, non-linear pharmacokinetics and unpredictable absorption require regular therapeutic monitoring of phenytoin. The influence of genetic differences, sex,age and race on the phenytoin plasma levels and its metabolites is well recognized. This study is aimed at evaluating phenytoin plasma drug concentration and its relationship with clinicalrespone, persistent seizures and toxicity in different gender and various age group of Chinese epileptic patients. This knowledge will help the clinicians in adjusting the drug dosages of phenytoin in various sub-groups of epileptic patients for enhancing the safety. efficacy and minimizing the toxicity of phenytoin. A total of 48 plasma samples of epileptic patients for measuring the olasma phenytoin concentration were received. Only patients displaying persistent seizures or suspected adverse effects were requested for drug monitoring. All these samples were analyzed for therapeutic drug monitoring with Enzyme-multiplied immunoassay technique. Suprisingly, it was found that majorities [85.5%] of samples were out of the reference range, of which 69% of samples were in sub-therapeutic levels and 16.5% of samples were above therapeutic levels. Only 14.5% of all samples had phenytoin levels in the therapeutic range. The difference in plasma concentration of phenytoin was notably altered in gender and various age groups. Careful attention must be applied to specific gender and particular age group on an individual basis in the interpretation of plasma concentration results, in order to facilitate the modification of doses and develop the best approach in treatment and to obtain the desired clinical response because multiple factors can effect the phenytoin plasma concentration. Through these results, it can be concluded that a good correlation exists between phenytoin plasma concentration and clinical response. Therefore, regular therapeutic monitoring of phenytoin and screening of HLA-A, B,C and DRB1 genotypes before prescribing phenytoin in epileptic patients is essentially required to achieve maximum clinical response and prevent the serious toxicity