PMID: 24713Apr 1, 1978

Fate of [14C]warfarin in guinea-pigs: effect of a concomitant single dose of salicylate

The Journal of Pharmacy and Pharmacology
L T WongB H Thomas

Abstract

When a single dose of sodium salicylate (177.8 mg kg-1, by mouth) was given with [14C] warfarin (1 mg kg-1, i.p.) to guinea-pigs, the salicylate depressed the blood concentrations of 14C for 6 h. At 1 h, salicylate increased the distribution of 14C in the liver and brain, but at 1 and 6 h it was decreased in the blood and kidney. A significant portion of the 14C was excreted into the bile, but was subject to enterohepatic circulation and then excreted by the kidney. There was an enhancement of the biliary elimination of 14C in the first 5 h after salicylate and a decrease in 14C concentration in blood; the proportion of warfarin to its metabolites excreted in the urine and bile was unchanged. Salicylate displaced serum protein bound [14C]warfarin in vitro. Salicylate increases the initial biliary elimination of warfarin by displacing some of that bound to plasma protein. This facilitated uptake of warfarin by the liver where it was metabolized. This effect of salicylate did not modify the hypoprothrombinaemia produced by warfarin.

References

Sep 2, 1971·The New England Journal of Medicine·J K Weser, E Sellers
Oct 1, 1972·Biochemical Pharmacology·B H ThomasH L Trenholm
Jun 1, 1974·Toxicology and Applied Pharmacology·B B ColdwellB H Thomas
May 1, 1970·The Journal of Clinical Investigation·R J Lewis, W F Trager
Nov 1, 1970·Journal of Medicinal Chemistry·W F TragerW A Garland

Citations

Jan 1, 1987·Reviews on Drug Metabolism and Drug Interactions·F A SutcliffeG G Gibson
Jun 14, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Matthew LindebladDouglas L Feinstein
Jul 21, 2020·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Masayuki SaitoTadashi Suzuki
Mar 1, 1980·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·L T Wong, G Solomonraj
Aug 1, 1987·The Journal of Pharmacy and Pharmacology·H H Thijssen, L G Baars
Dec 1, 1983·The Journal of Pharmacy and Pharmacology·H H ThijssenM J Reijnders

Related Concepts

Biliary Sludge
Serum Proteins
Drug Interactions
Cavia porcellus
Plasma Protein Binding Capacity
Thrombotest
Salicylic Acids
Drug or Chemical Tissue Distribution
Gen-Warfarin

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