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

Eur J Clin Pharmacol. 1977 Dec 28;12(6):457-61. doi: 10.1007/BF00561066.

Abstract

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.

MeSH terms

  • Administration, Oral
  • Adult
  • Coumarins / administration & dosage
  • Coumarins / blood
  • Coumarins / metabolism*
  • Female
  • Glucuronates / blood
  • Humans
  • Injections, Intravenous
  • Kinetics
  • Male
  • Middle Aged
  • Models, Biological

Substances

  • Coumarins
  • Glucuronates