Comparison of steady-state pharmacokinetics of valproic acid in children between monotherapy and multiple antiepileptic drug treatment

Chiba, Kazuhiro; Suganuma, Toshiyuki; Ishizaki, Takashi; Iriki, Tsukasa; Shirai, Yuko; Naitoh, Haruko; Hori, Makoto

doi:10.1016/s0022-3476(85)80097-4

Cited by 39 publications

(21 citation statements)

References 18 publications

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“…Previous studies have shown that concomitant therapy of VPA with other antiepileptic drugs increases VPA clearance in both adults and children as a consequence of their enzyme induction capacity [27,[32][33][34]. In agreement with these studies, the final CL regression model showed that PB, a known enzyme inducer that enhances the biotransformation of VPA [34,35], produces an increase of 28.9% in this parameter, which would imply the administration of higher valproate doses to achieve therapeutic concentrations.…”

Section: Discussionsupporting

confidence: 72%

Population pharmacokinetics of valproate in Mexican children with epilepsy

Corrêa

Rodríguez

Romano

2008

Biopharm & Drug Disp

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Section: Discussionsupporting

confidence: 72%

Population pharmacokinetics of valproate in Mexican children with epilepsy

Corrêa

Rodríguez

Romano

2008

Biopharm & Drug Disp

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“…Several studies have noted age‐related changes in the VPA pharmacokinetics of paediatric patients (3, 17, 18). Generally, VPA clearance increases with respect to weight in children, as compared with the adult population.…”

Section: Discussionmentioning

confidence: 99%

Valproate population pharmacokinetics in children

Serrano

Sánchez

Otero

et al. 1999

Journal of Clinical Pharmacy and Therapeutics

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“…The clearance of VPA, adjusted for weight, has been observed to decrease with age from childhood to adulthood [2][3][4]. The proportion of VPA excreted as oxidative metabolites appears to be increased in children relative to adults [1,5].…”

Section: Introductionmentioning

confidence: 99%

Urinary excretion of valproate metabolites in children and adolescents

Reith

Andrews

Parker

et al. 2000

Biopharm & Drug Disp

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The objective of this communication is to describe the changes in the metabolic profile of valproic acid (VPA) from early to late childhood and adolescence. A cross-sectional study of 12 children and adolescents attending a neurological outpatients department, who were medicated with VPA, was carried out. The proportions of daily dose excreted as VPA-glucuronide, 3-oxo-VPA and 4-OH-VPA were calculated by relating 24-h recovery of these metabolites from urine to daily VPA dose. VPA, 3-oxo-VPA and 2-en-valproic acid (2-en-VPA) were measured in trough serum samples. VPA and its metabolites were measured using a capillary gas chromatograpy method. The proportion of daily dose recovered as VPA-glucuronide in children 10 years and younger was smaller than in older children (p<0.05). There were no differences between age groups in the recovery of the other measured metabolites. Lamotrigine (LTG) comedication was also associated with a higher proportion of VPA dose recovered as glucuronide (p<0.01). LTG comedication had a stronger association with a higher proportion of dose being recovered as VPA-glucuronide on multivariate analysis than did the age group (p=0.001 versus p<0.05). In conclusion, older children and adolescents, when compared with younger children, and those comedicated with LTG excrete a higher proportion of VPA dose as VPA-glucuronide.

show abstract

Comparison of steady-state pharmacokinetics of valproic acid in children between monotherapy and multiple antiepileptic drug treatment

Cited by 39 publications

References 18 publications

Population pharmacokinetics of valproate in Mexican children with epilepsy

Population pharmacokinetics of valproate in Mexican children with epilepsy

Valproate population pharmacokinetics in children

Urinary excretion of valproate metabolites in children and adolescents

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