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Biomedical subjects

R Kaul

Publications and source records attributed to R Kaul.

At least 145 records · Page 8Linked to original sources
PubMed1982

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

With 14C-potassium cyanate as the starting material, 2-14C-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%).

Administration, Topical↗
PubMed1982

2-14C-1-Allyl-3,5-diethyl-6-chlorouracil II: Isolation and structures of the major sulfur-free and three minor sulfur-containing metabolites and mechanism of biotransformation.

The metabolites of 1-allyl-3,5-diethyl-6-chlorouracil in rabbit urine were isolated by preparative thick-layer, liquid-column, and gas chromatography. With the aid of mass and 1H-NMR spectra, and by comparison with an authentic sample, the major metabolite, 1, was identified as 6,8-diethyl-2-hydroxymethyl-tetrahydrooxazolo-[3,2-c]-pyrimidine-5,7(4H,6H)-dione, Metabolite 2 as 1-allyl-3-ethyl-5-(1-hydroxyethyl)-6-methylthiouracil, Metabolite 3 as 1-allyl-3,5-diethyl-6-methylthiouracil, and Metabolite 4 as 6,8-diethyl-2-hydroxymethyl-tetrahydrothiazolo-[3,2-c]pyrimidine-5,7(4H,6H)-dione. The mechanism of the formation of sulfur-containing metabolites is discussed, and a new metabolic pathway for the formation of methylthio compounds is proposed.

Animals↗
PubMed1982

Identification of the major degradation product of 1-propyl-3,5-diethyl-6-chlorouracil in rabbits and mechanism of the formation of bicyclic barbituric acid metabolites.

The major degradation product of 1-propyl-3,5-diethyl-6-chlorouracil in rabbits is identified as 6,8-diethyl-2-methyl-tetrahydrooxazolo[3,2-c]pyrimidine-5,7(4H,6H)-dione. The mechanism of the formation of this bicyclic barbituric acid derivative is discussed. The biotransformation takes place via substitution of the chlorine by beta- and not by alpha-hydroxy group of the intermediate hydroxypropane.

Animals↗
PubMed1980

2-14C-1-(2'-deoxy-beta-D-ribofuranosyl)-5-ethyluracil: synthesis and biotransformation in rats.

With 14C-urea as the starting material, 2-14C-1-(2'-deoxy-beta-D-ribofuranosyl)-5-ethyluracil [2-14C-beta-5-ethyl-2'-deoxyuridine] was synthesized for metabolic studies. After intravenous administration in rats, the radioactivity disappeared in the blood within 72 hr, being eliminated primarily in the urine (97%). The major elimination took place in the first 24 hr (92%). Little radioactivity was detected in the organs and tissues after 3 days. Approximately 50% of the urine radioactivity probably was due to an unidentified conjugate, 30% was due to Metabolite II, and 20% was unchanged drug. Metabolite II was identified as 5-ethyluracil by mass and 1H-NMR spectra and by comparison with an authentic sample.

Animals↗