Pharmacokinetics of total and free valproic acid during monotherapy in infants.

Abstract:

:The pharmacokinetics of free and total valproic acid (VPA) in plasma and whole blood after oral administration during steady state was investigated in seven infants (mean age 10.7 months) receiving monotherapy. The VPA concentrations in whole blood closely followed those in plasma but at a reduced level. A positive correlation was found between dose and mean plasma concentration (r = 0.71). Mean terminal half-lives were similar in plasma and whole blood (12.5 and 15.5 h, respectively), but were considerably longer than for free VPA (6.4 and 6.5 h, respectively; P less than 0.01). There was a significant decrease in half-lives with increasing age (P less than 0.05). Plasma and whole blood clearance for total VPA was higher than reported in older infants and adults (17.8 and 28.9 ml/kg per hour) and was considerably higher for free VPA (127.6 and 188.8 ml/kg per hour, respectively). The increase in clearance compared with that in older subjects is well in concordance with a lower protein binding of VPA (mean 85.3%). Of special importance is that the percentage of unbound VPA increased with increasing concentrations of total VPA. The fraction of unbound VPA in plasma increased even more in subjects with low albumin concentrations (P less than 0.01).

journal_name

J Neurol

journal_title

Journal of neurology

authors

Herngren L,Lundberg B,Nergårdh A

doi

10.1007/BF00315328

subject

Has Abstract

pub_date

1991-09-01 00:00:00

pages

315-9

issue

6

eissn

0340-5354

issn

1432-1459

journal_volume

238

pub_type

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