Evaluation of carbamazepine and carbamazepine-epoxide protein binding in patients undergoing epilepsy surgery

Carbamazepine (CBZ) serum concentrations increase after epilepsy surgery. A possible mechanism may be acute changes in protein binding, specifically those involving the acute phase reactant alpha(1)-acid glycoprotein (AAG). We prospectively evaluated 16 adults (11 receiving CBZ) with epilepsy (mean age 30 +/- 9.9 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, ALB, CBZ, and CBZ-E free fractions were determined before surgery (baseline) and on postoperative days 1-5, 14, and 30. AAG was measured with a radial immunodiffusion assay method, CBZ and CBZ-E serum concentrations were determined by high-performance liquid chromatography (HPLC). Free fractions of CBZ 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 for 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/gl) and decreasing to baseline levels between days 14 and 30. CBZ serum concentrations were significantly increased in the immediate postoperative period (day 3), but albumin concentrations and CBZ and CBZ-E free fractions did not differ significantly between baseline and the postoperative time points. Temporal lobe resection results in an acute phase reaction which is manifested in part by significant changes in AAG. Although CBZ and CBZ-E total serum concentrations increased significantly in the immediate postoperative period, epilepsy surgery did not appear to result in significant overall changes in drug binding to plasma proteins.