title: Erythromycin effects on multiple-dose carbamazepine kinetics.
abstract: To determine the effects of erythromycin on multiple-dose carbamazepine pharmacokinetics, seven healthy male volunteers were given 300-400 mg of carbamazepine each morning for 17 consecutive days. All subjects were given a placebo erythromycin form every 6 h on days 12, 13, and 14, then changed to erythromycin base 250 mg every 6 h for the final 3 days. Serial blood samples were drawn after the morning doses on days 14 and 17. Analysis of carbamazepine and carbamazepine-10,11-epoxide concentrations were made by high-performance liquid chromatography. Pharmacokinetic analysis showed carbamazepine half-life and 24-h postdose concentration to increase significantly (p less than 0.05) and oral clearance to decrease (p less than 0.05) during erythromycin administration. Decreases in carbamazepine-10,11-epoxide Cmax (p less than 0.001), area under the concentration-time curve0-24 (p less than 0.001), and carbamazepine-10,11-epoxide to carbamazepine ratio (p less than 0.01) also occurred during carbamazepine dosing. Erythromycin significantly inhibits the epoxide-diol metabolic pathway by which carbamazepine is transformed to carbamazepine-10,11-epoxide. Wide individual variability in this interaction should serve to warn practitioners of the unpredictability of this interaction.
authors.affiliation: Department of Pharmacy Practice, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
authors.forename: M V
authors.initials: MV
authors.lastname: Miles
authors.forename: M B
authors.initials: MB
authors.lastname: Tennison
mesh_terms: D000042:Absorption; D000328:Adult; D002220:Carbamazepine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004917:Erythromycin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male
chemical_list: D002220:Carbamazepine; D004917:Erythromycin