Multiple factors affecting excretion of warfarin in rats. 1977

E S Pepper, and W D Wosilait

Dialysis studies showed that the binding of warfarin by rat serum decreased in the presence of either tolbutamide or oxyphenbutazone. A combination of tolbutamide and oxyphenbutazone decreased the binding of warfarin more than either of the drugs separately. The binding of warfarin by serum from fasted rats was less than in controls, presumably from competition between free fatty acids (FFA) and warfarin for the same site(s) on albumin. The binding of warfarin further decreased under the combined effect of fasting and the presence of tolbutamide than under either condition alone. The binding of warfarin was less at 37 degrees C than 23 degrees C and even less at 37 degrees C in the presence of a combination of tolbutamide and oxyphenbutazone. When tolbutamide or oxyphenbutazone was injected 60 min after iv injection of 14C-warfarin there was an increase in the rate of biliary flow, the amount of radioactivity, and its excretion rate in bile. Injecting both drugs at 60 min further increased these variables.

UI MeSH Term Description Entries
D008297 Male Males
D010113 Oxyphenbutazone A non-steroidal anti-inflammatory drug. Oxyphenbutazone eyedrops have been used abroad in the management of postoperative ocular inflammation, superficial eye injuries, and episcleritis. (From AMA, Drug Evaluations Annual, 1994, p2000) It had been used by mouth in rheumatic disorders such as ankylosing spondylitis, osteoarthritis, and rheumatoid arthritis but such use is no longer considered justified owing to the risk of severe hematological adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p27) Hydroxyphenylbutazone,Diflamil,Oxyphenylbutazone,Tanderil
D003956 Dialysis A process of selective diffusion through a membrane. It is usually used to separate low-molecular-weight solutes which diffuse through the membrane from the colloidal and high-molecular-weight solutes which do not. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Dialyses
D005215 Fasting Abstaining from FOOD. Hunger Strike,Hunger Strikes,Strike, Hunger,Strikes, Hunger
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001646 Bile An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum. Biliary Sludge,Sludge, Biliary
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D013696 Temperature The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms. Temperatures
D014044 Tolbutamide A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290) Apo-Tolbutamide,Artosin,Diabetol,Diaval,Dolipol,Orabet,Orinase,Rastinon,Tolbutamid R.A.N.
D014859 Warfarin An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. 4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one,Aldocumar,Apo-Warfarin,Coumadin,Coumadine,Gen-Warfarin,Marevan,Tedicumar,Warfant,Warfarin Potassium,Warfarin Sodium,Potassium, Warfarin,Sodium, Warfarin

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