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. 1984 Nov;18(5):655–662. doi: 10.1111/j.1365-2125.1984.tb02526.x

Plasma disposition of vitamin K1 in relation to anticoagulant poisoning.

B K Park, A K Scott, A C Wilson, B P Haynes, A M Breckenridge
PMCID: PMC1463546  PMID: 6508974

Abstract

The disposition of vitamin K1, after intravenous (10 mg) and oral doses (10 mg and 50 mg) was studied in six healthy male subjects. After intravenous administration, the plasma concentration-time profile was adequately fitted with an average terminal half-life of 1.7 h. After oral administration (10 mg and 50 mg) the availability of vitamin K showed marked inter-individual variation (10-63%). With the higher dose intra-individual variation was also observed. Experiments in brodifacoum-anticoagulated rabbits demonstrate that the duration of action of a pharmacological dose (10 mg/kg) is short (9 h) and that high plasma concentrations (ca 1 microgram/ml) of the vitamin are required to drive clotting factor synthesis during maximum coumarin anticoagulation. Taken collectively, these data indicate that the short duration of action of vitamin K, frequently observed in cases of coumarin poisoning, is a consequence of requirements for high vitamin K concentrations and rapid clearance of the vitamin.

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Selected References

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

  1. Barkhan P., Shearer M. J. Metabolism of vitamin K1 (phylloquinone) in man. Proc R Soc Med. 1977 Feb;70(2):93–96. doi: 10.1177/003591577707000211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barlow A. M., Gay A. L., Park B. K. Difenacoum (Neosorexa) poisoning. Br Med J (Clin Res Ed) 1982 Aug 21;285(6341):541–541. doi: 10.1136/bmj.285.6341.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bechtold H., Trenk D., Meinertz T., Rowland M., Jähnchen E. Cyclic interconversion of vitamin K1 and vitamin K1 2,3-epoxide in man. Br J Clin Pharmacol. 1983 Dec;16(6):683–689. doi: 10.1111/j.1365-2125.1983.tb02241.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bell R. G., Matschiner J. T. Warfarin and the inhibition of vitamin K activity by an oxide metabolite. Nature. 1972 May 5;237(5349):32–33. doi: 10.1038/237032a0. [DOI] [PubMed] [Google Scholar]
  5. Bell R. G. Metabolism of vitamin K and prothrombin synthesis: anticoagulants and the vitamin K--epoxide cycle. Fed Proc. 1978 Oct;37(12):2599–2604. [PubMed] [Google Scholar]
  6. Bell R. G., Sadowski J. A., Matschiner J. T. Mechanism of action of warfarin. Warfarin and metabolism of vitamin K 1 . Biochemistry. 1972 May 9;11(10):1959–1961. doi: 10.1021/bi00760a034. [DOI] [PubMed] [Google Scholar]
  7. Bjornsson T. D., Blaschke T. F. Vitamin K1 disposition and therapy of warfarin overdose. Lancet. 1978 Oct 14;2(8094):846–847. doi: 10.1016/s0140-6736(78)92633-8. [DOI] [PubMed] [Google Scholar]
  8. Bjornsson T. D., Meffin P. J., Swezey S. E., Blaschke T. F. Effects of clofibrate and warfarin alone and in combination on the disposition of vitamin K1. J Pharmacol Exp Ther. 1979 Sep;210(3):322–326. [PubMed] [Google Scholar]
  9. Duello T. J., Matschiner J. T. Characterization of vitamin K from human liver. J Nutr. 1972 Mar;102(3):331–335. doi: 10.1093/jn/102.3.331. [DOI] [PubMed] [Google Scholar]
  10. Frick P. G., Riedler G., Brögli H. Dose response and minimal daily requirement for vitamin K in man. J Appl Physiol. 1967 Sep;23(3):387–389. doi: 10.1152/jappl.1967.23.3.387. [DOI] [PubMed] [Google Scholar]
  11. Haroon Y., Hauschka P. V. Application of high-performance liquid chromatography to assay phylloquinone (vitamin K1) in rat liver. J Lipid Res. 1983 Apr;24(4):481–484. [PubMed] [Google Scholar]
  12. Hollander D. Vitamin K1 absorption by everted intestinal sacs of the rat. Am J Physiol. 1973 Aug;225(2):360–364. doi: 10.1152/ajplegacy.1973.225.2.360. [DOI] [PubMed] [Google Scholar]
  13. Kasimis B. S., Spiers A. S. Thrombotic complications in patients with advanced prostatic cancer treated with chemotherapy. Lancet. 1979 Jan 20;1(8108):159–159. doi: 10.1016/s0140-6736(79)90553-1. [DOI] [PubMed] [Google Scholar]
  14. Leck J. B., Park B. K. A comparative study of the effects of warfarin and brodifacoum on the relationship between vitamin K1 metabolism and clotting factor activity in warfarin-susceptible and warfarin-resistant rats. Biochem Pharmacol. 1981 Jan 15;30(2):123–128. doi: 10.1016/0006-2952(81)90182-9. [DOI] [PubMed] [Google Scholar]
  15. Matschiner J. T., Taggart W. V. Bioassay of vitamin K by intracardial injection in deficient adult male rats. J Nutr. 1968 Jan;94(1):57–59. doi: 10.1093/jn/94.1.57. [DOI] [PubMed] [Google Scholar]
  16. Nielsen-Kudsk F. A pharmacokinetic program for TI-59. J Pharmacol Methods. 1980 Jun;3(4):345–355. doi: 10.1016/0160-5402(80)90076-5. [DOI] [PubMed] [Google Scholar]
  17. O'Reilly R. A., Aggeler P. M. Covert anticoagulant ingestion: study of 25 patients and review of world literature. Medicine (Baltimore) 1976 Sep;55(5):389–399. doi: 10.1097/00005792-197609000-00003. [DOI] [PubMed] [Google Scholar]
  18. O'Reilly R. A. Vitamin K and the oral anticoagulant drugs. Annu Rev Med. 1976;27:245–261. doi: 10.1146/annurev.me.27.020176.001333. [DOI] [PubMed] [Google Scholar]
  19. Park B. K., Leck J. B. A comparison of vitamin K antagonism by warfarin, difenacoum and brodifacoum in the rabbit. Biochem Pharmacol. 1982 Nov 15;31(22):3635–3639. doi: 10.1016/0006-2952(82)90587-1. [DOI] [PubMed] [Google Scholar]
  20. Park B. K., Leck J. B., Wilson A. C., Serlin M. J., Breckenridge A. M. A study of the effect of anticoagulants on [3H]vitamin K1 metabolism and prothrombin complex activity in the rabbit. Biochem Pharmacol. 1979 Apr 15;28(8):1323–1329. doi: 10.1016/0006-2952(79)90433-7. [DOI] [PubMed] [Google Scholar]
  21. Serlin M. J., Sibeon R. G., Mossman S., Breckenridge A. M., Williams J. R., Atwood J. L., Willoughby J. M. Cimetidine: interaction with oral anticoagulants in man. Lancet. 1979 Aug 18;2(8138):317–319. doi: 10.1016/s0140-6736(79)90340-4. [DOI] [PubMed] [Google Scholar]
  22. Shearer M. J., Mallinson C. N., Webster G. R., Barkhan P. Clearance from plasma and excretion in urine, faeces and bile of an intravenous dose of tritiated vitamin K 1 in man. Br J Haematol. 1972 May;22(5):579–588. doi: 10.1111/j.1365-2141.1972.tb05704.x. [DOI] [PubMed] [Google Scholar]
  23. Shearer M. J., McBurney A., Barkhan P. Studies on the absorption and metabolism of phylloquinone (vitamin K1) in man. Vitam Horm. 1974;32:513–542. doi: 10.1016/s0083-6729(08)60025-4. [DOI] [PubMed] [Google Scholar]
  24. Stenflo J., Suttie J. W. Vitamin K-dependent formation of gamma-carboxyglutamic acid. Annu Rev Biochem. 1977;46:157–172. doi: 10.1146/annurev.bi.46.070177.001105. [DOI] [PubMed] [Google Scholar]
  25. Whitlon D. S., Sadowski J. A., Suttie J. W. Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. Biochemistry. 1978 Apr 18;17(8):1371–1377. doi: 10.1021/bi00601a003. [DOI] [PubMed] [Google Scholar]
  26. Willingham A. K., Matschiner J. T. Changes in phylloquinone epoxidase activity related to prothrombin synthesis and microsomal clotting activity in the rat. Biochem J. 1974 Jun;140(3):435–441. doi: 10.1042/bj1400435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wilson A. C., Park B. K. Quantitative analysis of pharmacological levels of vitamin K1 and vitamin K1 2,3-epoxide in rabbit plasma by high-performance liquid chromatography. J Chromatogr. 1983 Oct 14;277:292–299. doi: 10.1016/s0378-4347(00)84847-1. [DOI] [PubMed] [Google Scholar]
  28. Wiss O., Gloor H. Absorption, distribution, storage, and metabolites of vitamins K and related quinones. Vitam Horm. 1966;24:575–586. doi: 10.1016/s0083-6729(08)60222-8. [DOI] [PubMed] [Google Scholar]

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