The clinical pharmacology of 5-trifluoromethyl-2'-deoxyuridine.

Clinical pharmacological studies of trifluorothymidine (F3TdR)-2-14C, which include analyses of respiratory CO2, urine, and plasma, have been completed on eight patients with advanced cancer. Various dose levels and methods of administration were studied. The only metabolites detected in urine and serum samples were unchanged F3TdR, trifluorothymine, and 5-carboxyuracil. No 14CO2 was produced, a result consistent with studies done with mice, showing that this pyrimidine ring is not degraded in vivo . The half-life in the serum of F3TdR given i.v. was 18 min at 27 mg/kg/day. There was measurable binding of labeled material to the serum proteins. One- and 2-hr urine samples of 12 additional patients treated with F3TdR have been analyzed to determine whether the amount of undegraded F3TdR in the early urine specimens could serve as a guide to the possible clinical effectiveness of the drug in these individual patients. The results indicate that there is no correlation between the extent of catabolism of F3TdR and its clinical efficacy. The 1st- and 2nd-hr urines of eight pediatric patients were studied, and the children metabolized the drug less rapidly than did adults.