European Journal of Clinical Pharmacology

, Volume 12, Issue 6, pp 457–461 | Cite as

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

  • W. A. Ritschel
  • M. E. Brady
  • H. S. I. Tan
  • K. A. Hoffmann
  • I. M. Yiu
  • K. W. Grummich
Originals

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.

Key words

Coumarin 7-Hydroxycoumarin drug disposition first-pass effect bioavailability 

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Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • W. A. Ritschel
    • 1
  • M. E. Brady
    • 1
  • H. S. I. Tan
    • 1
  • K. A. Hoffmann
    • 2
  • I. M. Yiu
    • 1
  • K. W. Grummich
    • 1
  1. 1.College of PharmacyUniversity of Cincinnati Medical CenterCincinnatiUSA
  2. 2.Department of AnesthesiaJewish HospitalCincinnatiUSA

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