First-Dose and Steady-State Pharmacokinetics of Valproic Acid in Children with Seizures
- 1 January 1983
- journal article
- review article
- Published by Springer Nature in Clinical Pharmacokinetics
- Vol. 8 (5), 447-455
- https://doi.org/10.2165/00003088-198308050-00005
Abstract
The serum concentration-time curve of valproic acid was followed in 25 children after single oral doses of the drug and at steady-state. Total body clearance (CL), half-life (t½), and apparent volume of distribution (Vd) were calculated from the terminal portion of the curve and from the area under the serum concentration-time curve (AUC). The CL and Vd were significantly greater at steady-state (0.42 ± 0.20 ml/min/kg and 0.231 ± 0.067 L/kg, respectively) than after a single dose (0.32 ± 0.13 ml/min/kg and 0.191 ± 0.055 L/kg, respectively). This difference was most pronounced in patients with valproic acid dosage increases in excess of 20% and no change in their concurrent anticonvulsant therapy between the single-dose and steady-state study periods. The t½ was not significantly different between the 2 study periods. There was a significant correlation between age and both CL and Vd after single doses and at steady-state. The t½ did not appear to be age related. These results suggest that the adequacy of the dosage regimen must be determined during maintenance therapy rather than extrapolated from data obtained after a single dose. Re-evaluation of therapy as the child grows older may also be necessary in view of the age-related differences in valproic acid pharmacokinetics which this study has demonstrated.This publication has 11 references indexed in Scilit:
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