PMID: 1195101Oct 1, 1975Paper

Comparative pharmacokinetics of coumarin anticoagulants. XIV: relationship between protein binding, distribution, and elimination kinetics of warfarin in rats

Journal of Pharmaceutical Sciences
A Yacobi, G Levy

Abstract

The relationships between the protein binding, distribution in the body, and kinetics of elimination of warfarin were studied. Individual rats eliminated warfarin by apparent first-order kinetics, with a biological half-life of 5.9-41 hr and a total plasma clearance of 2.4-22 ml kg(-1) hr(-1). There is a strong positive correlation between the apparent volume of distribution (Vd) and the elimination rate constant (kel). There was no apparent concentration dependance of warfarin binding to serum proteins over a wide concentration range, but there were pronounced intersubject variations in protein binding, with the free fraction of drug (f) in serum ranging from 0.172 x 10(-2) to 1.53 x 10(-2). There are strong positive correlations between f and kel, f and Vd, and f and the kidney-serum concentration ratio of warfarin. Consistent with theory, there is an excellent positive linear correlation between f and total plasma clearance of the drug. The intersubject variation in f is not related to variations in serum albumin or total protein concentration. There is a strong correlation between values of f for serum and liver homogenate in individual animals, consistent with the lack of correlation between f in serum and the liver-serum ...Continue Reading

References

Jun 1, 1974·Journal of Pharmacokinetics and Biopharmaceutics·A Yacobi, G Levy
May 1, 1974·Journal of Pharmaceutical Sciences·G Levy, A Yacobi
May 1, 1968·Acta Medica Scandinavica·K PyöräläG Myllylä
Jan 1, 1969·Journal of Pharmaceutical Sciences·W J Jusko, G Levy
Apr 1, 1967·The American Journal of Medicine·R J LewisT H Spaet
Oct 1, 1963·The Journal of Clinical Investigation·R A O'REILLYL S LEONG

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Citations

Apr 17, 1979·European Journal of Clinical Pharmacology·D FremstadS Jacobsen
Jan 1, 1977·European Journal of Clinical Pharmacology·S Husted, F Andreasen
Mar 17, 1978·European Journal of Clinical Pharmacology·F AndreasenE Mikkelsen
Jan 1, 1981·European Journal of Clinical Pharmacology·E M Faed
Dec 18, 1978·European Journal of Clinical Pharmacology·B Fichtl, H Kurz
Jan 1, 1981·European Journal of Clinical Pharmacology·M Gibaldi, J R Koup
Jul 30, 1978·European Journal of Clinical Pharmacology·M Gibaldi, P J McNamara
Dec 17, 2011·European Journal of Drug Metabolism and Pharmacokinetics·Kotsiou AntoniaChristine Tesseromatis
Apr 28, 1980·Life Sciences·A YacobiG Levy
Nov 24, 1986·Life Sciences·D M Cocchetto, T D Bjornsson
Jan 1, 1981·Pharmacology & Therapeutics·J G Wagner
Jan 1, 1987·Reviews on Drug Metabolism and Drug Interactions·F A SutcliffeG G Gibson
Jan 1, 1983·Drug Metabolism Reviews·G R Wilkinson
Jan 1, 1983·Drug Metabolism Reviews·P G Dayton, J E Sanders
Aug 1, 1976·Journal of Pharmaceutical Sciences·F W Goodhart, M L Eichman
Jan 1, 1996·Drug Metabolism and Drug Interactions·L A Damani, I P Nnane
Oct 1, 1980·Toxicology and Applied Pharmacology·D L Barber, H W Colvin
Oct 1, 1989·Acta Anaesthesiologica Scandinavica·R CalvoJ M Rodriguez-Sasiaín
Dec 1, 1983·British Journal of Clinical Pharmacology·I H BenedekP J McNamara
Jul 1, 1977·Journal of Pharmaceutical Sciences·J T Slattery, G Levy
Aug 1, 1977·Journal of Pharmaceutical Sciences·M Gibaldi, P J McNamara
Oct 1, 1977·Journal of Pharmacokinetics and Biopharmaceutics·T D BjornssonT F Blaschke
Apr 1, 1988·Journal of Pharmacokinetics and Biopharmaceutics·S C TsaoM Hanano
Jul 1, 1981·Biopharmaceutics & Drug Disposition·H L BehmJ G Wagner
Jan 1, 1976·Annals of the New York Academy of Sciences·G Levy
Apr 1, 1983·Journal of Pharmacokinetics and Biopharmaceutics·D G CovellM Berman
Apr 1, 1977·Journal of Pharmacokinetics and Biopharmaceutics·A Yacobi, G Levy
Aug 1, 1977·Acta Pharmacologica Et Toxicologica·D FremstadK M Lunde
Dec 1, 1975·Journal of Pharmacokinetics and Biopharmaceutics·A Yacobi, G Levy
Feb 1, 1988·Journal of Pharmacokinetics and Biopharmaceutics·D TrenkS Oie
Dec 1, 1983·The Journal of Pharmacy and Pharmacology·H H ThijssenM J Reijnders
Apr 1, 1980·Journal of Pharmacokinetics and Biopharmaceutics·D Trenk, E Jähnchen

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