Abstract
Commonly used conventional antiepileptic drugs for pharmacotherapy in epilepsy are phenytoin, carbamazepine and valproic acid. These drugs have complex pharmacokinetic properties leading to fluctuation in their plasma level at given same therapeutic dose. The present study was done to monitor their plasma levels. A prospective observational study was conducted at National Public Health Laboratory. After taking detail history, blood samples were taken from epileptic patients of all age groups and both gender who were on usual therapeutic dose of one or two combined antiepileptic drugs. Plasma level of these drugs were analyzed by using Fluorescence Polarization Immuno Assay (FPIA) technique. Out of total 417 testing, 81 were tested for phenytoin , 241 for carbamazepine and 95 for valproic acid. Their levels were further analyzed to find therapeutic, subtherapeutic and toxic levels. Out of total 81 blood samples tested for phenytoin, 38.8% had plasma drug at therapeutic level, 38.8% at subtherapeutic level and 28.4% had toxic level. Carbamazepine was tested in 241 samples and 79.3% cases had at therapeutic drug level, 15.8% had subtherapeutic drug level and 4.9% had toxic level. Out of 95 samples tested for valproic acid, 62% had therapeutic level and 20% had subtherapeutic and 18% had toxic level of drug. Therapeutic drug monitoring of phenytoin showed wide fluctuation in its plasma level. Its toxic and subtherapeutic levels were quite high. It is suggested that the dose of phenytoin should be adjusted after regular plasma level monitoring only. Monitoring of carbamazepine and valproic acid were also helpful when their toxicity and efficacy are doubtful.
Highlights
Phenytoin, carbamazepine and valproic acid are the commonly used conventional antiepileptic drugs
Shakya et al Therapeutic Drug Monitoring of Antiepileptic Drugs valproic acid cause enzyme inhibition. These have complex pharmacokinetic properties leading to wide fluctuation in their plasma concentration, interaction potential with other drugs and narrow therapeutic index which can lead to toxic effects or loss of therapeutic efficacy.[5,6]
A prospective observational study was carried out at Natoinal Public Health Laboratory (NPHL) from Jan 1, 2007 to Jun 31, 2007. It included epileptic patients of both gender and age groups, ranging from 11 months to 90 years who were on usual therapeutic dose of one or two antiepileptic drugs and attended NPHL for drug analysis
Summary
Carbamazepine and valproic acid are the commonly used conventional antiepileptic drugs (AED for pharmacotherapy in epileptic patients.[1] Therapeutic drug monitoring (TDM) of their blood levels are useful to check compliance and to confirm suspected toxicity. Phenytoin was introduced in 1938, carbamazepine in 1962 and valproic acid in 1978 as AEDs.[2,3,4] All of those exhibit non-linear kinetics. Shakya et al Therapeutic Drug Monitoring of Antiepileptic Drugs valproic acid cause enzyme inhibition. These have complex pharmacokinetic properties leading to wide fluctuation in their plasma concentration, interaction potential with other drugs and narrow therapeutic index (phenytoin and carbamazepine) which can lead to toxic effects or loss of therapeutic efficacy.[5,6] Monitoring of phenytoin is essential. The present study was conducted to monitor the plasma level of these drugs
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