Abstract
A preliminary clinical observation suggests the possibility of changes in valproate level when coadministered with guanfacine. Two pediatric inpatients (8 and 9 years of age) were treated with valproic acid and guanfacine concurrently. In one child, when guanfacine was tapered and discontinued, the plasma valproate concentration decreased by 41% from 128 μg/mL to 76 μg/mL. In the other case, studied in an ABA design, the child exhibited a rapid increase in plasma valproate levels while guanfacine was administered. It is proposed that guanfacine may affect the pharmacokinetics of valproic acid and lead to a significant increase in valproate plasma levels when used concurrently with this agent. The mechanism of this proposed interaction may involve drug–drug competition at the level of hepatic glucuronidation (conjugation), although shifts in protein binding cannot be ruled out.
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