Influence of age and co-medication on the steady-state pharmacokinetics of valproic acid in Tunisian patients with epilepsy.
OBJECTIVE
Valproic acid (VPA) is a widely prescribed broad-spectrum antiepileptic drug. However, the use of VPA is complicated in clinical practice by its remarkably wide variability of pharmacokinetics. The objective of this study was to investigate the effects of demographic factors and associated therapies on steady-state plasma VPA concentrations in patients with epilepsy.


METHODS
This retrospective cohort study was carried out using the routine therapeutic drug monitoring (TDM) database. Stepwise logistic regression analysis was used to compare serum VPA levels in 78 epilepsy patients treated with VPA in association with at least one other drug that could have interacted with CYP2C9, CYP2C19 or UGT enzymes.


RESULTS
The frequency of subtherapeutic serum VPA levels was significantly increased with younger age (P<0.02), the number of co-medications (P<0.007) and use of enzyme-inducing co-medications (P<0.02). No significant correlations between VPA dose and trough plasma concentrations were found, as the latter did not increase in proportion to the dose.


CONCLUSIONS
Routine monitoring of VPA serum levels would be extremely useful in epilepsy patients in the pediatric age group and in those who require associated enzyme-inducing medications.
University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029, Tunisia. Electronic address: benmahmoud_lobna@medecinesfax.org.
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Ben Mahmoud
University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029, Tunisia.
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A
Hakim
University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029, Tunisia.
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H
Ghozzi
University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029, Tunisia.
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Atheymen
University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029, Tunisia.
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Sahnoun
University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029, Tunisia.
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K
Zeghal
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D020536:Enzyme Activators / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019338:Polypharmacy; D012189:Retrospective Studies; D014635:Valproic Acid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
D000927:Anticonvulsants; D020536:Enzyme Activators; D014635:Valproic Acid
Drug interaction; Therapeutic drug monitoring; Valproic acid