Effect of erythromycin on carbamazepine kinetics

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Abstract
Two recent reports of carbamazepine-induced intoxication during concurrent therapy with macrolide antibiotics prompted a carefully controlled 2-way cross-over study in 8 healthy male nonsmokers. Treatment A was 250 mg erythromycin every 6 h for 5 days before and 3 days after 400 mg carbamazepine [an anticonvulsant]. Treatment B was 400 mg of carbamazepine alone. 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 h after the carbamazepine dose were assayed in duplicate by HPLC [high performance liquid chromatography]. The data were fit to a 1-compartment open model with 1st-order absorption and elimination. Clearance of oral carbamazepine was lower in the presence of erythromycin (mean, 0.290 .+-. 0.074 and 0.360 .+-. 0.072 1/kg per day). There were no differences in apparent volume of distribution (1.01 .+-. 0.20 and 1.04 .+-. 0.12 1/kg), 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 2 treatment groups. The decrease in clearance of oral carbamazepine secondary to erythromycin indicates that further clinical studies are warranted.

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