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A case is reported in which dramatic decreases in the protein binding of Phenytoin and phenobarbital were noted. A 57-year-old burn patient with a history of a seizure disorder had increased free fractions of phenytoin and phenobarbital. The patient later developed renal failure and the free fractions of both drugs were further increased. Decreases in the protein binding of Phenytoin in patients with hypoalbuminemia and/or uremia have been well documented, but the effects of these conditions on phenobarbital protein binding have not been well studied. In the case described here, the presence of both hypoalbuminemia and uremia were necessary before a doubling of the free fraction of phenobarbital was noted. Although it is not a highly protein-bound drug, in some circumstances protein binding alterations of phenobarbital may be of clinical significance.

The single-dose prediction model (SDPM) of Slattery et al. has been shown accurately to predict short-term (3 to 7 days) steady-state valproic acid (VPA) concentrations in normal volunteers and in hospitalized patients receiving monotherapy. To assess the long-term usefulness of the SDPM in a real-life clinic setting, six ambulatory patients ranging in age from 2 to 8 years were studied. Blood samples were drawn at least 6 h after the initial dose but before the second dose of VPA. A steady-state trough concentration (Cmin) was measured 3 to 7 days after the initiation of therapy. Dosage adjustments and alterations in therapeutic regimen were allowed and another Cminwas measured after 1 to 12 months. Predicted Cmin, values were calculated for both the short-term and long-term VPA regimens. Predictive performance analysis demonstrated that the SDPM was unbiased in predicting both short-term and long-term VPA Cmin, values and precise in predicting only short-term VPA Cminn, values. The SDPM is not a reliable predictor of long-term total VPA concentrations in seizure patients in an outpatient clinic setting.