title: Increased plasma valproate concentrations when coadministered with guanfacine.
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 microg/mL to 76 microg/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.
authors.affiliation: Division of Child and Adolescent Psychiatry, Allegheny University of the Health Sciences, Eastern Pennsylvania Psychiatric Institute, Philadelphia 19129, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Ambrosini
authors.forename: R M
authors.initials: RM
authors.lastname: Sheikh
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000009:adverse effects*; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000523:psychology; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000188:drug therapy / Q000523:psychology; D002648:Child; D004347:Drug Interactions; D005260:Female; D016316:Guanfacine / Q000009:adverse effects*; D006801:Humans; D008297:Male; D014635:Valproic Acid / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000316:Adrenergic alpha-Agonists; D000927:Anticonvulsants; D016316:Guanfacine; D014635:Valproic Acid