Because of these changes in valproate clearance , monitoring of antiepileptic concentrations should be intensified whenever concomitant antiepileptics are introduced or withdrawn. Neonates - Children within the first two months of life have a markedly decreased ability to eliminate valproate compared to older children and adults. For example, in one study, the half-life in children under 10 days ranged from 10 to 67 hours compared to a range of 7 to 13 hours in children greater than 2 months. Over the age of 10 years, children have pharmacokinetic parameters that approximate those of adults. Accordingly, the initial dosage should be reduced in the elderly.
Liver disease impairs the capacity to eliminate valproate.
In that study, the half-life of valproate was increased from 12 to 18 hours. Accordingly, monitoring of total concentrations may be misleading since free concentrations may be substantially elevated in patients with hepatic disease whereas total concentrations may appear to be normal. Therefore, no dosage adjustment appears to be necessary in patients with renal failure. The relationship between plasma concentration and clinical response is not well documented. One contributing factor is the nonlinear, concentration dependent protein binding of valproate which affects the clearance of the drug.