Metabolism and excretion of paclitaxel after oral administration in combination with cyclosporin A and after i.v. administration

The objective of this study was to compare the quantitative excretion of pa clitaxel and metabolites after i.v. and oral drug administration. Four pati ents received 800 mg/m(2) paclitaxel orally 30 min after 15 mg/kg oral cycl osporin A, co-administered to enhance the uptake of paclitaxel. Three weeks later these and three other patients received 175 mg/m(2) paclitaxel by i. v. infusion. Blood samples, urine and feces were collected up to 48-96 h af ter administration, and analyzed for paclitaxel and metabolites. The area u nder the plasma concentration-time curve of paclitaxel after i.v, administr ation (175 mg/m(2)) was 16.2+/-1.7 muM . h and after oral administration (3 00 mg/m(2)) 3.8 +/- 1.5 muM . h. Following i.v. infusion of paclitaxel, tot al fecal excretion was 56+/-25%, with the metabolite 6 alpha -hydroxypaclit axel being the main excretory product (37+/-18%). After oral administration of paclitaxel, total fecal excretion was 76+/-21%, Df which paclitaxel acc ounted for 61+/-14%. In conclusion, after i.v. administration of paclitaxel , excretion occurs mainly in the feces with the metabolites as the major ex cretory products, orally administered paclitaxel is also mainly excreted in feces but with the parent drug in highest amounts. We assume that this hig h amount of parent drug is due to incomplete absorption of orally administe red paclitaxel from the gastrointestinal tract. [(C) 2000 Lippincott Willia ms & Wilkins.].