Phenobarbital and carbamazepine concentrations were determined by the EMIT technique in tears, saliva, cerebrospinal fluid (CSF), and plasma of patients with epilepsy. Closer correlation was shown between tear/plasma and tear/CSF ratios than between saliva/plasma and saliva/CSF ratios for the two agents. The phenobarbital CSF/serum ratio was in good agreement with data in the literature, and the higher ratio found for carbamazepine may be caused by an EMIT assay cross-reaction for the free fraction of carbamazepine-10,11-epoxide. In our hands, tears seem to represent the best practical indicator of the unbound fraction of an anticonvulsant drug, and the noninvasiveness of the method makes it specifically useful in pediatric neurology.
Anticonvulsant therapy was stopped in 191 epileptic children (109 males and 82 females) after a seizure-free period of at least 2 years, independent of EEG findings, followed up for a minimum of 2 years after withdrawal. Overall, 43 (22.5 %) had recurrence of seizures; of these, 79% relapsed within the 1st year after drug stopping and 93% within the 2nd year. The probability of remaining seizure free was 97% at the end of the withdrawal period, 82% 1 year later, 79% at 2 years and 77% at 5 years. In order to evaluate the risk of recurrence and the predictive factors of relapse, several parameters were investigated by univariate and multivariate statistical analysis. At univariate analysis, the factors which proved to be significantly correlated to relapses were: age at onset over 4 years, seizure-free time less than 2 years, sudden drug discontinuation, pathological EEG records during seizure-free time and paroxysmal responses to intermittent photic stimulation (IPS). At multivariate analysis, only age at onset, seizure-free time and sudden discontinuation were the factors indicating a significantly higher relapse risk; paroxysmal IPS responses, when analyzed in association with these variables, proved to be significant and increased the predictive value for prognosis of associated factors.
Valproic acid (VPA) was determined by EMIT assay in plasma, tears, saliva, and cerebrospinal fluid (CSF) of patients with epilepsy. Closer correlation was shown between tear/plasma and tear/CSF ratios than between saliva/plasma and saliva/CSF ratios. The VPA CSF/serum ratio was in good agreement with data in the literature. Salivary levels were extremely erratic, while those for tears were much more reliable. Determination of VPA in tears is therefore the best method of studying the VPA free fraction in those cases in which investigations of protein binding of the drug are necessary.
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