EVALUATION OF CARBAMAZEPINE AND CARBAMAZEPINE-EPOXIDE PROTEIN-BINDINGIN PATIENTS UNDERGOING EPILEPSY SURGERY

Carbamazepine (CBZ) serum concentrations increase after epilepsy surge ry. A possible mechanism may be acute changes in protein binding, spec ifically those involving the acute phase reactant alpha(1)-acid glycop rotein (AAG). We prospectively evaluated 16 adults(ll receiving CBZ) w ith epilepsy (mean age 30 +/- 8.9 years, 8 women and 8 men) undergoing temporal lobe resections and characterized AAG, albumin, CBZ, and CBZ -epoxide (CBZ-E) free fractions over time. AAG, ALE, CBZ, and CBZ-E fr ee fractions were determined before surgery (baseline) and on postoper ative days 1-5, 14, and 30. AAG was measured with a radial immunodiffu sion assay method, CBZ and CBZ-E serum concentrations were determined by high-performance liquid chromatography (HPLC). Free fractions of CB Z and CBZ-E: were calculated as the ratio of unbound (determined after ultracentrifugation) to total serum drug concentrations. Statistical analysis included analysis of variance (ANOVA) and Student's t test fo r paired data when appropriate, with significance assigned at p < 0.05 . All data are mean +/- SD. AAG concentrations increased significantly from baseline (61.9 +/- 21.3 mg/dl), peaking at postoperative day 3 ( 116.8 +/- 20.6 mg/dl) and decreasing to baseline levels between days 1 4 and 30. CBZ serum concentrations were significantly increased in the immediate postoperative period (day 3), but albumin concentrations an d CBZ and CBZ-E free fractions did not differ significantly between ba seline and the postoperative time points. Temporal lobe resection resu lts in an acute phase reaction which is manifested in part by signific ant changes in AAG. Although CBZ and CBZ-E total serum concentrations increased significantly in the immediate postoperative period, epileps y surgery did not appear to result in significant overall changes in d rug binding to plasma proteins.