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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1979 Sep;8(3):243–247. doi: 10.1111/j.1365-2125.1979.tb01009.x

Pharmacokinetics and pharmacodynamics of warfarin at steady state.

P A Routledge, P H Chapman, D M Davies, M D Rawlins
PMCID: PMC1429794  PMID: 497091

Abstract

1 The relationship between warfarin dose, total and free plasma warfarin concentration, and anticoagulant effect was examined at several steady-state levels in fifteen patients during withdrawal of warfarin therapy. 2 Total plasma clearance was significantly correlated with the free fraction in plasma (r=0.955). 3 There was an age related decline in the dose of warfarin, and in the total and free plasma warfarin concentrations required to produce the same anticoagulant effect. However, neither total nor free plasma warfarin clearances varied with age. 4 Individual patients' log concentration-effect relationships were linear above a prothrombin ratio of 1.2 and there was a significant correlation (r=-0.586) between the slope and the free fraction of warfarin in plasma. It is suggested that plasma protein binding may reflect the interaction between warfarin and its effector site in the hepatocyte.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aggeler P. M., O'Reilly R. A. The pharmacological basis of oral anticoagulant therapy. Thromb Diath Haemorrh Suppl. 1966;21:227–256. [PubMed] [Google Scholar]
  2. Breckenridge A., Orme M. Kinetics of warfarin absorption in man. Clin Pharmacol Ther. 1973 Nov-Dec;14(6):955–961. doi: 10.1002/cpt1973146955. [DOI] [PubMed] [Google Scholar]
  3. Gibaldi M., McNamara P. J. Tissue binding of drugs. J Pharm Sci. 1977 Aug;66(8):1211–1212. doi: 10.1002/jps.2600660846. [DOI] [PubMed] [Google Scholar]
  4. Levy G., Yacobi A. Letter: Effect of plasma protein binding on elimination of warfarin. J Pharm Sci. 1974 May;63(5):805–806. doi: 10.1002/jps.2600630539. [DOI] [PubMed] [Google Scholar]
  5. Lewis R. J., Ilnicki L. P., Carlstrom M. The assay of warfarin in plasma or stool. Biochem Med. 1970 Dec;4(5):376–382. doi: 10.1016/0006-2944(70)90065-7. [DOI] [PubMed] [Google Scholar]
  6. Lewis R. J., Trager W. F., Chan K. K., Breckenridge A., Orme M., Roland M., Schary W. Warfarin. Stereochemical aspects of its metabolism and the interaction with phenylbutazone. J Clin Invest. 1974 Jun;53(6):1607–1617. doi: 10.1172/JCI107711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Mitchell A. A. Smoking and warfarin dosage. N Engl J Med. 1972 Nov 30;287(22):1153–1154. [PubMed] [Google Scholar]
  8. Nagashima R., O'Reilly R. A., Levy G. Kinetics of pharmacologic effects in man: the anticoagulant action of warfarin. Clin Pharmacol Ther. 1969 Jan-Feb;10(1):22–35. doi: 10.1002/cpt196910122. [DOI] [PubMed] [Google Scholar]
  9. O'Reilly R. A. Studies on the coumarin anticoagulant drugs: interaction of human plasma albumin and warfarin sodium. J Clin Invest. 1967 May;46(5):829–837. doi: 10.1172/JCI105582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Rawlins M. D., Collste P., Frisk-Holmberg M., Lind M., Ostman J., Sjöqvist F. Steady-state plasma concentrations of alprenolol in man. Eur J Clin Pharmacol. 1974 Aug 23;7(5):353–356. doi: 10.1007/BF00558205. [DOI] [PubMed] [Google Scholar]
  11. Shepherd A. M., Hewick D. S., Moreland T. A., Stevenson I. H. Age as a determinant of sensitivity to warfarin. Br J Clin Pharmacol. 1977 Jun;4(3):315–320. doi: 10.1111/j.1365-2125.1977.tb00719.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Wagner J. G., Northam J. I., Alway C. D., Carpenter O. S. Blood levels of drug at the equilibrium state after multiple dosing. Nature. 1965 Sep 18;207(5003):1301–1302. doi: 10.1038/2071301a0. [DOI] [PubMed] [Google Scholar]
  13. Yacobi A., Levy G. Comparative pharmacokinetics of coumarin anticoagulants XXVIII: Predictive identification of rats with relatively steep serum warfarin concentration-anticoagulatnt response characteristics. J Pharm Sci. 1977 Jan;66(1):145–146. doi: 10.1002/jps.2600660145. [DOI] [PubMed] [Google Scholar]
  14. Yacobi A., Levy G. Protein binding of warfarin enantiomers in serum of humans and rats. J Pharmacokinet Biopharm. 1977 Apr;5(2):123–131. doi: 10.1007/BF01066216. [DOI] [PubMed] [Google Scholar]
  15. Yacobi A., Udall J. A., Levy G. Serum protein binding as a determinant of warfarin body clearance and anticoagulant effect. Clin Pharmacol Ther. 1976 May;19(5 Pt 1):552–558. doi: 10.1002/cpt1976195part1552. [DOI] [PubMed] [Google Scholar]

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