ABSTRACT
Three groups of non-smoking epileptic patients without liver disease receiving antiepileptic monotherapy have been compared with 10 healthy non-smoking volunteers. Group 1 received phenytoin (n = 10), Group 2 carbamazepine (n = 10) and Group 3 valproic acid (n = 6). Cytochrome P-450 activity was monitored by measuring urinary 6-beta-hydroxycortisol output and systemic antipyrine clearance. Both, 6-beta-hydroxycortisol output and antipyrine clearance were significantly enhanced in patients on phenytoin and carbamazepine, but not in those on valproic acid. On the other hand, phenytoin alone increased the clearance of caffeine from 1.5 (controls) to 3.6 ml.min-1.kg-1, and reduced its half life from 4.8 to 2.4 h. Carbamazepine and valproic acid had no effect on caffeine metabolism. The results are in keeping with the well known heterogeneity of the hepatic monooxygenase system, as phenytoin and carbamazepine induce different panels of cytochrome P-450 isoenzymes. Phenytoin treatment may impair the validity of the caffeine liver function test.
Subject(s)
Caffeine/pharmacokinetics , Carbamazepine/pharmacology , Phenytoin/pharmacology , Valproic Acid/pharmacology , Adolescent , Adult , Aged , Antipyrine/pharmacokinetics , Caffeine/blood , Cytochrome P-450 Enzyme System/biosynthesis , Enzyme Induction/drug effects , Epilepsy/metabolism , Female , Half-Life , Humans , Hydrocortisone/analogs & derivatives , Hydrocortisone/blood , Male , Middle AgedSubject(s)
Clonazepam/therapeutic use , Diazepam/therapeutic use , Epilepsy, Absence/drug therapy , Adolescent , Adult , Aged , Child , Clonazepam/adverse effects , Diazepam/adverse effects , Electroencephalography , Evoked Potentials/drug effects , Female , Humans , Male , Middle Aged , Prospective Studies , Random AllocationABSTRACT
The recently available ultrafiltration technique facilitates determination of the free drug serum concentration of several antiepileptic drugs. For this reason a reappraisal of the clinical significance of free level monitoring was thought necessary. In this study on 203 patients receiving carbamazepine monotherapy and 101 patients receiving valproic acid monotherapy, the total and free drug levels were correlated with therapeutic outcome and side effects. Our investigations indicated no closer correlation between free concentration and seizure reduction or side effects than between total concentration and effectiveness or side effects. However, we found a close correlation between total and free concentrations.
