Disposition of the hypolipidaemic agent, 6-amino-2-mercapto-5-methylpyrimidine-4-carboxylic acid, in Sprague-Dawley rats.
The disposition of [2-14C]6-amino-2-mercapto-5-methylpyrimidine-4-carboxylic acid has been determined in rats following intravenous and oral administration. A two-compartment pharmacokinetic model fitted to the blood and urinary data predicted its maximum terminal (beta) half-life to be 38 h. Urinary and faecal excretion accounted for approximately 30 and 8% of the administered radioactivity, respectively. The parent compound accounted for 88% of the urine radioactivity after oral administration. In a tissue distribution study, the largest percentages of radioactivity were found in the skin and carcass; by 24 h, all other organs contained less than 1% of the administered radioactivity. The drug was highly water soluble, not extensively bound to plasma proteins, nor taken up by red blood cells. The drug uptake by human fibroblasts or rat aorta cells appeared to be by passive diffusion.
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360.
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Hall
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Wong
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Wyrick
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Simlot
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Shrewsbury
D000284:Administration, Oral; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D005753:Gastric Mucosa / Q000378:metabolism; D006207:Half-Life; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D011485:Protein Binding; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D001798:Blood Proteins; D000960:Hypolipidemic Agents; D011743:Pyrimidines; C070934:6-amino-2-mercapto-5-methylpyrimidine-4-carboxylic acid