The objective of this study was to compare the quantitative excretion of paclitaxel and metabolites after i.v. and oral drug administration. Four patients received 300 mg/m2 paclitaxel orally 30 min after 15 mg/kg oral cyclosporin A, co-administered to enhance the uptake of paclitaxel. Three weeks later these and three other patients received 175 mg/m2 paclitaxel by i.v. infusion. Blood samples, urine and feces were collected up to 48-96 h after administration, and analyzed for paclitaxel and metabolites. The area under the plasma concentration-time curve of paclitaxel after i.v. administration (175 mg/m2) was 16.2 +/- 1.7 microM x h and after oral administration (300 mg/m2) 3.8 +/- 1.5 microM x h. Following i.v. infusion of paclitaxel, total fecal excretion was 56 +/- 25%, with the metabolite 6alpha-hydroxypaclitaxel being the main excretory product (37 +/- 18%). After oral administration of paclitaxel, total fecal excretion was 76 +/- 21%, of which paclitaxel accounted for 61 +/- 14%. In conclusion, after i.v. administration of paclitaxel, excretion occurs mainly in the feces with the metabolites as the major excretory products. Orally administered paclitaxel is also mainly excreted in feces but with the parent drug in highest amounts. We assume that this high amount of parent drug is due to incomplete absorption of orally administered paclitaxel from the gastrointestinal tract.