DISPOSITION OF THE CARCINOSTATIC AGENT 1-(2-CHLOROETHYL)-3-[1'-(5'-PARA-NITROBENZOYL-2',3'-ISOPROPYLIDENE)-ALPHA, "BETA-D-RIBOFURANOSYL]-1-NITROSOUREA IN ANIMALS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (9) , 3351-3356
Abstract
The disposition of 1-(2-chloroethyl)-3-[1''-(5''-p-nitrobenzoyl-2'',3''-isopropylidene)-.alpha.,.beta.-D-ribofuranosyl]-1-nitro-sourea (RFCNU) was investigated in animals following i.p. administration (35 .mu.mol/kg) of the drug labeled with 14C in 3 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 2 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-14 C]- or [carbonyl-14C]RFCNU. 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.