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Pharmacokinetics of coumarin and its 7-hydroxy-metabolites upon intravenous and peroral administration of coumarin in man

European Journal of Clinical Pharmacology volume 12, pages 457–461 (1977)Cite this article

Summary

The pharmacokinetics of coumarin (C) upon i.v. and p.o. administration and its metabolites 7-hydroxy-coumarin (7-HC) and 7-hydroxy-coumarin glucuronide (7-HCG) have been studied. Six healthy volunteers were involved in this investigation. Four of the volunteers participated in a crossover study. Coumarin was administered i.v. and p.o. in dose sizes of 0.25 mg/kg and 0.857 mg/kg, respectively. Coumarin is rapidly absorbed p.o., however the availability to systemic circulation is less than 4%. The rest of the dose appears quantitatively as 7-HC and 7-HCG in systemic circulation suggesting an extensive firstpass effect. Coumarin and 7-HCG are best fitted to an open two-compartment model, whereas 7-HC is best fitted to an open one-compartment model. The biological half-life of both C (0.80 vs. 1.02 h) and 7-HCG (1.47 vs. 1.15 h) was not significantly different for the two routes of administration. The large total clearance of C again suggests a first-pass effect; while that of 7-HCG, which is nearly exclusively eliminated into urine, indicates active tubular secretion of the glucuronide.

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Authors and Affiliations

  1. College of Pharmacy, University of Cincinnati Medical Center, 45267, Cincinnati, Ohio, USA

    W. A. Ritschel, M. E. Brady, H. S. I. Tan, I. M. Yiu & K. W. Grummich

  2. Department of Anesthesia, Jewish Hospital, 45229, Cincinnati, Ohio, USA

    K. A. Hoffmann

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  1. W. A. Ritschel
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  2. M. E. Brady
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  3. H. S. I. Tan
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  4. K. A. Hoffmann
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  5. I. M. Yiu
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  6. K. W. Grummich
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Ritschel, W.A., Brady, M.E., Tan, H.S.I. et al. Pharmacokinetics of coumarin and its 7-hydroxy-metabolites upon intravenous and peroral administration of coumarin in man. Eur J Clin Pharmacol 12, 457–461 (1977). https://doi.org/10.1007/BF00561066

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  • DOI: https://doi.org/10.1007/BF00561066

Key words

  • Coumarin
  • 7-Hydroxycoumarin
  • drug disposition
  • first-pass effect
  • bioavailability