[Protein binding of fenpentadiol-14C (2-méthyl-4-p-chlorophényl-2,4-pentane-diol) in vivo and in vitro (author's transl)]. / Etude in vivo et in vitro des liaisons protéiniques du fenpentadiol-14C (2-méthyl-4-p-chlorophényl-2,4-pentane-diol).

ABSTRACT

The binding of 14C-fenpentadiol to plasma proteins of different species in vivo and in vitro was studied using equilibrium dialysis. In vivo, the binding rate, in rat, was found to be 30%. In the pig, this rate varied as a function of time from 10.8% 15 minutes after drug administration to 20.4% 6 hours later. In vitro, the binding rate was found to be a function of the drug concentration and ranged from 57 to 36% at concentrations of from 0.4 to 11 micrograms/ml. No significant differences were observed between the two species. In human plasma, the in vitro binding rate was found to range from 34 to 18.4% for concentrations of 11 to 200 micrograms/ml. Under the same conditions, but using 10 mg of human albumin incubated in varying concentrations of the drug (50 to 800 micrograms/ml), the binding rate ranged from 8.4 to 4%. The binding rate seemed also to be a function of the pH of the medium with the pH of 11 yielding a maximum binding rate. Scatchard analysis of the in vitro human albumin data gave the following values K = 4.7 X 10(3) M-1, n = 1.5. When human alpha-globulin was used, the protein binding values varied from 9.1 to 4.3% at drug concentrations from 50 to 40 micrograms/ml. When human beta- and gamma-globulins were used, no binding was found to occur. In vitro, incubation of the drug in whole blood of either rat or pig gave a value of 20% drug fixed in erythrocytes. In vivo, in the rat, this value was found to be 60%.