Disposition of the carcinostatic agent 1-(2-chloroethyl)-3-[1'-(5'-p-nitrobenzoyl-2',3'-isopropylidene)-alpha,beta-d-ribofuranosyl]-1-nitrosourea in animals.

The disposition of 1-(2-chloroethyl)-3-[1'(5'-p-nitrobenzoyl-2',3'-isopropylidene)-alpha,beta-D-ribofuranosyl]-1-nitrosourea (RFCNU) was investigated in animals following i.p. administration (35 micromol/kg) of the drug labeled with 14C in three different positions. The appearance and disappearance kinetics of the label in blood and plasma were strongly dependent upon the labeled species administered to animals. Protein binding of [carboxyl-14C]- and [carbonyl-14C]RFCNU greatly prolonged the blood and plasma half-life of these two labeled species. No intact RFCNU was found when rat plasma samples were analyzed using high-performance liquid chromatography, indicating the very short half-life of this compound. Most of the dose was recovered in the urine after administration of the carboxyl-14C and ethyl-14C species and in the expired air as 14CO2 after administration of the carbonyl-14C species. Except for the liver and kidney, no specific localization of the radioactivity was found when animals were given [carboxyl-14C]- or [carbonyl-14C]RFCNU. However, tissue distribution studies showed a marked specificity of the species carrying the ethyl-14C moiety for the liver, kidney, pancreas, and thymus, but not for the brain.