Pharmacokinetics of coumarin and 7-hydroxycoumarin in the rhesus monkey after intravenous and peroral administration.

Coumarin (C, Venalot) and 7-hydroxycoumarin (7-OHC) were administered in a dose of 1 mg/kg to rhesus monkeys intravenously and perorally. The concentrations of C, 7-OHC and their metabolite, 7-hydroxycoumarin glucuronide (7-OHCG) were measured in whole blood. The terminal half-life, t1/2, the apparent distribution volume, Vd, and the total clearance, CL, of C and 7-OHC after i.v. administration are 1.64 +/- 0.41 h and 0.8 +/- 0.29 h, 2.55 +/- 0.95 l/kg and 6.96 +/- 3.44 l/kg, and 19.05 +/- 5.41 ml/min/kg and 103.7 +/- 34.4 ml/min/kg (mean +/- SEM), respectively. The rates of absorption of C and 7-OHC are 12.8 +/- 2.38 and 4.62 +/- 1.08 h-1, respectively. The rate of metabolism of C via 7-OHC to 7-OHCG is 7.96 +/- 2.16 h-1 and that of 7-OHC to 7-OHCG is 27.99 +/- 11.73. The p.o. absolute bioavailability is 45 +/- 14% for C and 17.0 +/- 5% for 7-OHC. The pharmacokinetics of C in the rhesus monkey are similar to that in the dog. In man the p.o. absolute bioavailability is only 3.4%.