TAXOL METABOLISM AND DISPOSITION IN CANCER-PATIENTS

The objective of this study was to determine the metabolic fate and di sposition of taxol in cancer patients. Five patients received 225 or 2 50 mg/m(2) of taxol together with 100 mu Ci of [H-3]taxol as a 3-hr in fusion, followed by cisplatin and 5-fluorouracil. Urine, feces, and bl ood samples were collected for 120 hr and analyzed for total radioacti vity, taxol, and metabolites by reversed-phase HPLC and tandem MS. Tot al urinary excretion was 14.3 +/- 1.4% (SE) of the dose, with unchange d taxol and an unknown polar metabolite as the main excretion products . Total fecal excretion was 71.1 +/- 8.2%, with 6 alpha-hydroxytaxol b eing the largest component by far. Unchanged taxol and four other meta bolites could also be identified from fecal extracts. The plasma area under the curve for unchanged taxol was 20.5 +/- 2.3 mu M . hr and tha t for total taxol metabolites was 14.2 +/- 4.5 mu M . hr. The half-lif e of total metabolites (5.6 +/- 0.4 hr), however, greatly exceeded tha t of unchanged taxol (2.9 +/- 0.3 hr). Thus, at 5-hr posttaxol infusio n, the plasma concentrations of the five metabolites together exceeded the taxol concentration by 2.4-fold. The findings from this study sho uld be of importance as a guide to further therapeutic evaluation of t his drug.