2-/sup 14/C-1-Allyl-3,5-diethyl-6-chlorouracil I: Synthesis, absorption in human skin, excretion, distribution, and metabolism in rats and rabbits

Journal Article · Sun Aug 01 04:00:00 EDT 1982 · J. Pharm. Sci.; (United States)

DOI:https://doi.org/10.1002/jps.2600710813· OSTI ID:6562774

Kaul, R; Hempel, B; Kiefer, G

With /sup 14/C-potassium cyanate as the starting material, 2-/sup 14/C-1-allyl-3,5-diethyl-6-chlorouracil was synthesized for in vitro and in vivo absorption studies in human skin and for metabolic studies in rats and rabbits. The radioactivity in the horny layer, epidermis, and dermis of the human skin was determined after different intervals of time, and the radioactivity excreted in the urine was measured by collecting samples for 5 days from a patient and also under occlusion conditions. Almost 90% of the radioactivity remained on the surface and approximately 6.28% penetrated and was systemically absorbed. Over a 5-day period, a total of 3.25% was excreted. Almost 3% was systemically absorbed and cumulated in the system. After intraperitoneal application in male and female rats, most of the radioactivity was excreted in the feces and urine, with female rats excreting more in the urine than male rats. The radioactivity rose in the organs in the first 3 hr and then decreased. At the end of 144 hr, no appreciable radioactivity could be found in the organs and tissues, except in the carcass where the cumulation was maximum (1%). After intravenous injection in rabbits, most of the radioactivity (80%) was excreted in the urine and only 4% in the feces. At the end of 96 hr, approximately 3% was cumulated in the body. The drug was quantitatively metabolized in both rats and rabbits: Metabolite 1 (70-85%), Metabolite 2 (10-15%), Metabolite 3 (5-10%), and Metabolite 4 (0.3%).

• Research Organization: Research Laboratories, Pharmaceuticals Robugen GmbH, Esslingen, West Germany
• OSTI ID: 6562774
• Journal Information: J. Pharm. Sci.; (United States), Journal Name: J. Pharm. Sci.; (United States) Vol. 71:8; ISSN JPMSA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ABSORPTION
ANIMALS
AZINES
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CARBON 14 COMPOUNDS
CLEARANCE
DISTRIBUTION
EXCRETION
FECES
FEMALES
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IN VITRO
IN VIVO
INJECTION
INTAKE
INTRAPERITONEAL INJECTION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MALES
MAMMALS
MAN
MATERIALS
METABOLITES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PRIMATES
PYRIMIDINES
RABBITS
RATS
RODENTS
SKIN ABSORPTION
TRACER TECHNIQUES
UPTAKE
URACILS
URINE
URINE MAN
VERTEBRATES
WASTES