skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: 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

Abstract

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%more » 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%).« less

Authors:
; ;
Publication Date:
Research Org.:
Research Laboratories, Pharmaceuticals Robugen GmbH, Esslingen, West Germany
OSTI Identifier:
6562774
Resource Type:
Journal Article
Journal Name:
J. Pharm. Sci.; (United States)
Additional Journal Information:
Journal Volume: 71:8
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 59 BASIC BIOLOGICAL SCIENCES; URACILS; EXCRETION; URINE MAN; SKIN ABSORPTION; CARBON 14 COMPOUNDS; IN VITRO; IN VIVO; TRACER TECHNIQUES; URINE; MAN; FECES; FEMALES; INTRAPERITONEAL INJECTION; MALES; METABOLITES; RABBITS; RATS; ABSORPTION; ANIMALS; AZINES; BIOLOGICAL MATERIALS; BIOLOGICAL WASTES; BODY FLUIDS; CLEARANCE; DISTRIBUTION; HETEROCYCLIC COMPOUNDS; HYDROXY COMPOUNDS; INJECTION; INTAKE; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; MAMMALS; MATERIALS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; PRIMATES; PYRIMIDINES; RODENTS; UPTAKE; VERTEBRATES; WASTES; 560306* - Chemicals Metabolism & Toxicology- Man- (-1987); 560305 - Chemicals Metabolism & Toxicology- Vertebrates- (-1987); 550501 - Metabolism- Tracer Techniques

Citation Formats

Kaul, R, Hempel, B, and Kiefer, G. 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. United States: N. p., 1982. Web. doi:10.1002/jps.2600710813.
Kaul, R, Hempel, B, & Kiefer, G. 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. United States. https://doi.org/10.1002/jps.2600710813
Kaul, R, Hempel, B, and Kiefer, G. 1982. "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". United States. https://doi.org/10.1002/jps.2600710813.
@article{osti_6562774,
title = {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},
author = {Kaul, R and Hempel, B and Kiefer, G},
abstractNote = {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%).},
doi = {10.1002/jps.2600710813},
url = {https://www.osti.gov/biblio/6562774}, journal = {J. Pharm. Sci.; (United States)},
number = ,
volume = 71:8,
place = {United States},
year = {Sun Aug 01 00:00:00 EDT 1982},
month = {Sun Aug 01 00:00:00 EDT 1982}
}