Effect of erythromycin on carbamazepine kinetics

Two recent reports of carbamazepine-induced intoxication during concurrent therapy with macrolide antibiotics prompted us to perform a carefully controlled two-way cross-over study in eight healthy male nonsmokers. Treatment A was 250 mg erythromycin every 6 hr for 5 days before and 3 days after 400 mg carbamazepine. Treatment B was 400 mg of carbamazepine alone. One half of the subjects received treatment A, then B, while the other half received treatment B, then A. There was a 4-wk washout period between treatments. Plasma samples obtained at various times up to 72 hr after the carbamazepine dose were assayed in duplicate by HPLC. The data were fit to a one-compartment open model with first-order absorption and elimination. Clearance of oral carbamazepine was lower in the presence of erythromycin (mean +/- SD, 0.290 +/- 0.074 and 0.360 +/- 0.072 1 X kg-1 X day-1). There were no differences in apparent volume of distribution (1.01 +/- 0.20 and 1.04 +/- 0.12 1 X kg-1), elimination rate constant (0.302 +/- 0.113 and 0.348 +/- 0.079 day-1), or absorption rate constant (14.5 +/- 8.7 and 15.5 +/- 16.6 day-1) between the two treatment groups. The decrease in clearance of oral carbamazepine secondary to erythromycin indicates that further clinical studies are warranted.