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Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma.

This report describes the binding of 70 synthetic compounds to both testosterone-binding globulin (TeBG) and corticosteroid-binding globulin (CBG). The ability of each compound to displace [3H]testosterone from TeBG and [3H]cortisol from CBG adsorbed from a plasma pool onto a solid phase matrix of Concanavalin A-Sepharose was determined under equilibrium conditions at physiological pH and temperature. From these data, the association constants of the compounds for binding to both TeBG and CBG were calculated and used to predict whether endogenous steroid transport would be altered by the therapeutic administration of the drug. Computer simulation predicted that by interacting with TeBG, therapeutic levels of danazol, methyltestosterone, fluoxymesterone, and norgestrel could displace 83%, 48%, 43%, and 16%, respectively, of the concentration of testosterone bound to TeBG in a normal man. Similarly, by interacting with CBG, therapeutic levels of prednisolone could decrease the concentration of cortisol bound to CBG by approximately 32% in both men and women, and despite relatively low affinity binding to TeBG (5 X 10(5) M-1), prednisolone could also displace small amounts of testosterone from TeBG. These results indicate that binding to steroid transport proteins should be considered among the in vivo effects of drugs on endogenous steroid hormone levels.