phenprocoumon and 6-beta-hydroxycortisol

The effect of probenecid on the pharmacokinetics of phenprocoumon (PPC) given as a single oral or intravenous dose, on the vitamin-K-dependent protein-C-antigen, and on the pharmacokinetics of antipyrine and 6 beta-hydroxycortisol was determined in 14 healthy volunteers. Probenecid caused a 75% decrease in urinary excretion of PPC and PPC-glucuronide and shortened the plasma half-life of PPC significantly (by about 35%). The results after oral and intravenous administration of PPC did not differ significantly. Plasma protein-C-antigen concentrations following intravenous PPC were significantly increased by probenecid. The plasma half-life of antipyrine after 7 days of probenecid therapy was significantly diminished. Accordingly, urinary excretion of 6 beta-hydroxycortisol was significantly increased. These data appear for the first time to reveal enzyme-inducing properties of probenecid, which may be responsible for the shortening of PPC plasma half-life when probenecid is given simultaneously. In addition, the influence of probenecid on plasma protein-C-antigen concentrations may indicate further effects of probenecid on liver metabolism.

Topics: 4-Hydroxycoumarins; Adult; Antigens; Antipyrine; Humans; Hydrocortisone; Liver; Phenprocoumon; Probenecid; Protein C