Relation between plasma levels of valproic acid alone and its efficacy and toxicity in pediatric patients under chronic treatment
Armijo, J.A.; Valiente, R.; Herranz, J.L.
Archivos de Farmacologia y Toxicologia 7(1): 49-56
1981
ISSN/ISBN: 0304-8616 PMID: 6798945 Document Number: 175584
The therapeutic range of 50-100 .mu.g/ml for valproic acid may not be valid for several reasons. This range was established in combination with other anti-epileptic agents, and was based on studies in patients resistant to other anti-epileptic treatments. It was also based on a variety of types of epilepsy and ages and there was uncertainty about the time blood samples were taken. A new study on valproic acid was undertaken in 69 children ranging from 13 mo. to 3 yr, 11 mo. and suffering from various types of epilepsy. All received 3 daily doses of sodium valproate by mouth, some as syrup and others in tablet form. Treatment began with low doses, which were increased progressively to 50 .mu.g/ml and maximal doses close to 100 .mu.g/ml. Within these ranges, doses were readjusted according to need (epileptic crises vs. side effects). With the doses of sodium valproate used (32.7 .+-. 7.9 mg/kg body weight), the plasma levels determined were 54.1 .+-. 14.1 .mu.g/ml in 55 patients in whom blood samples were taken before the 1st dose in the morning and 93.5 .+-. 15.8 .mu.g/ml in 49 patients whose blood samples were taken 1.1/2 h after the dose. The total theoretical equilibrium concentration in 69 patients was 63.0 .+-. 15.2 .mu.g/ml. The correlation between the dose administered and the equilibrium concentration in each patient was very low. In 49 of the 69 patients (72%) the crises were completely suppressed.