Pharmacokinetics of phenprocoumon.

The pharmacokinetics of phenprocoumon was studied in 24 healthy volunteers between the ages of 23 and 28 years and a mean body weight of 72 kg by intraindividual comparison of the plasma level after i.v. and oral administration of 9 mg phenprocoumon (PPC) or by the evaluation of the total plasma clearance of PPC by simultaneous measurement of the urinary excretion and of the plasma concentration after the administration of 9 mg PPC. The following mean data were obtained after i.v. injection:t1/2 alpha 0.432h, t1/2 beta 128 h, co 0.651 microgram/ml, Vd 14.41,AUCo-omega 121 micrograms x h/ml. After intake of 9 mg PPC the following mean values were measured: tmax 2.25 h, Cmax 1.01 micrograms/ml, tabs 0.553 h, co 0.865 micrograms/ml, t1/2 beta 132 h, AUC0-infinity 164 micrograms x h/ml. By comparison of the PPC plasma level with the corresponding urinary excretion, a total mean PPC clearance of 20.0 (i.v.) and 15.1 (per os) ml/h was calculated within the first 8 h post dose, while the values measured did not differ between 8 and 48 h post dose (14.8 vs 15.3 ml/h). The steep decline in plasma level after i.v. injection of PPC might be caused by an enhanced renal and hepatic elimination of the free drug to a higher degree than after oral intake, while no differences existed between both modes of administration during the phase of elimination. A nearly total absorption of PPC from the tablet formulation is suggested.