Elevated free fractions of valproic acid in a heart transplant patient with hypoalbuminemia

OBJECTIVE: To report a case demonstrating the importance of monitoring unbo und valproic acid (VPA) serum concentrations in a patient with hypoalbumine mia. CASE SUMMARY: A 53-year-old white woman status-post heart transplantation w as admitted to the hospital for declining cardiac function, possible reject ion, and increased lethargy requiring intubation. An extensive workup of th e 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 p rompted the measurement of unbound serum concentrations of VPA. The VPA dos age was then adjusted based on the unbound rather than the total VPA serum concentration; the patient eventually improved and was discharged from the hospital. DISCUSSION: 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 incre ases in adverse effects, when dosage adjustments are based solely on measur ement of total VPA serum concentrations in patients with hypoalbuminemia. CONCLUSIONS: This case report suggests that appropriate monitoring of unbou nd drug concentrations of VPA may prevent unrecognized concentration-relate d adverse effects. Awareness of the pharmacokinetic relationship and advers e effects of VPA will aid clinicians in identifying the etiology of symptom s.