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- W1581856284 abstract "Summary The physiological disposition of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, a highly active agent against intraperitoneal and intracranial mouse leukemia L1210, was studied in mice, rats, dogs, and monkeys with the 14C label in each of 3 positions of the molecule, the ethylene, carbonyl, and cyclohexyl moieties. 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea is lipid soluble and, after parenteral dosage, rapidly degraded in mouse and dog plasma with 2 exponential phases. The half-life of the initial phase is about 5 min, while the 2nd phase extends over 1 hr. During the 6 hr after i.v. injection of ethylene-labeled 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in dogs, radioactivity in the cerebrospinal fluid exceeded that of plasma 3-fold. With the label in the cyclohexyl moiety, plasma radioactivity was about 50% of cerebrospinal fluid 14C levels. The drug following biotransformation is primarily excreted by the kidneys with excretion being essentially complete during the first 24 hr in rodents and monkeys, but more protracted in dogs. Biliary secretion and reabsorption from the gastrointestinal tract have been demonstrated. The cyclohexyl portion of the molecule was bound extensively (40 to 60%), while the ethylene moiety was not bound to plasma proteins of dogs. In mice, 10 to 20% of the carbonyl and 4 to 6% of ethylene carbon atoms were recovered in expired CO2 1 day after parenteral or oral dosage. The detection of cyclohexylamine, N, N′-dicyclohexylurea, among other predominant unidentified molecular species, supports the hypothesis of intermediate hydroxydiazoalkane and isocyanate formation during the degradation of nitrosoureas in vivo. However, the identified catabolites and cyclohexyl isocyanate were found to be inactive against the mouse leukemia L1210." @default.
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- W1581856284 date "1970-05-01" @default.
- W1581856284 modified "2023-09-23" @default.
- W1581856284 title "The absorption, distribution, excretion, and biotransformation of the carcinostatic 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in animals." @default.
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