title: Elevated free fractions of valproic acid in a heart transplant patient with hypoalbuminemia.
abstract: OBJECTIVE
  To report a case demonstrating the importance of monitoring unbound valproic acid (VPA) serum concentrations in a patient with hypoalbuminemia.
  
  
  METHODS
  A 53-year-old white woman status-post heart transplantation was admitted to the hospital for declining cardiac function, possible rejection, and increased lethargy requiring intubation. An extensive workup of the patient's profound lethargy was initiated, including an evaluation of her VPA regimen. Initially, VPA dosages were adjusted based on the total serum concentration of VPA. Hypoalbuminemia compounded with increased lethargy prompted the measurement of unbound serum concentrations of VPA. The VPA dosage was then adjusted based on the unbound rather than the total VPA serum concentration; the patient eventually improved and was discharged from the hospital.
  
  
  CONCLUSIONS
  Lethargy is a concentration-related adverse effect of VPA. The nonlinear pharmacokinetic and protein saturation characteristics of VPA may result in nonproportional elevations in unbound drug, and subsequent increases in adverse effects, when dosage adjustments are based solely on measurement of total VPA serum concentrations in patients with hypoalbuminemia.
  
  
  CONCLUSIONS
  This case report suggests that appropriate monitoring of unbound drug concentrations of VPA may prevent unrecognized concentration-related adverse effects. Awareness of the pharmacokinetic relationship and adverse effects of VPA will aid clinicians in identifying the etiology of symptoms.
authors.affiliation: Transplant Research Fellow, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Haroldson
authors.forename: L E
authors.initials: LE
authors.lastname: Kramer
authors.forename: D L
authors.initials: DL
authors.lastname: Wolff
authors.forename: K D
authors.initials: KD
authors.lastname: Lake
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood*; D001682:Biological Availability; D005260:Female; D016027:Heart Transplantation / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D012709:Serum Albumin / Q000172:deficiency*; D012894:Sleep Stages; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood*
chemical_list: D000927:Anticonvulsants; D012709:Serum Albumin; D014635:Valproic Acid