In eight healthy young volunteers, 15 g of activated charcoal administered orally 30 min after 50 mg of doxepin, reduced the achieved peak concentration of the drug in serum by 70% and total availability by 49%. Charcoal, 3 hours after the drug, did not significantly reduce absorption. When charcoal was administered 30 min after doxepin, the apparent elimination half-lives of doxepin and its main metabolite, desmethyldoxepin, were prolonged by 350 and 140%, respectively, suggesting gradual disaggregation of the charcoal-drug complex. Repeated doses of charcoal between 3 and 24 hours after doxepin increased significantly the apparent clearance of desmethyldoxepin. Repeated doses of charcoal may be beneficial in the treatment of overdosage with doxepin by preventing disaggregation of the drug from an initial dose of charcoal with subsequent absorption and reabsorption of parent drug and metabolites secreted into the gastrointestinal tract.