Gustavson L E, Benet L Z
J Pharmacokinet Biopharm. 1985 Dec;13(6):561-9. doi: 10.1007/BF01058901.
The macromolecular binding of prednisone has been studied in the plasma of eight healthy human volunteers. The subjects included two control males, two control females, two females taking estrogen-containing oral contraceptives, and two females in the third trimester of pregnancy. All volunteers exhibited the expected nonlinear plasma binding of prednisolone with free fraction increasing as the total prednisolone concentration was increased. Both the oral contraceptive and pregnant subjects had increased transcortin binding capacity over the control volunteers as evidenced by their increased binding of prednisolone. Prednisone macromolecular binding, however, was not altered by either changing total prednisone concentration or transcortin binding capacity. The mean prednisone free fraction was 0.250 +/- 0.027 in the eight subjects over the concentration range 0-2500 ng/ml. The addition of prednisolone in up to a 25-fold excess did not alter prednisone's free fraction. Prednisone apparently does not bind to transcortin with the same strong affinity that characterizes prednisolone's binding, and due to albumin's extensive binding capacity, prednisone macromolecular binding is not saturable over the pharmacological drug concentration range.
已对八名健康人类志愿者血浆中泼尼松的大分子结合情况进行了研究。受试者包括两名对照男性、两名对照女性、两名服用含雌激素口服避孕药的女性以及两名处于妊娠晚期的女性。所有志愿者均表现出预期的泼尼松龙血浆非线性结合，随着泼尼松龙总浓度的增加，游离分数升高。口服避孕药和怀孕受试者的皮质素结合能力均高于对照志愿者，这可从他们对泼尼松龙结合增加得到证明。然而，无论是改变泼尼松总浓度还是皮质素结合能力，泼尼松的大分子结合均未改变。在0 - 2500 ng/ml的浓度范围内，八名受试者中泼尼松的平均游离分数为0.250±0.027。加入高达25倍过量的泼尼松龙并不会改变泼尼松的游离分数。泼尼松显然不会以与泼尼松龙结合相同的强亲和力与皮质素结合，并且由于白蛋白具有广泛的结合能力，在药理药物浓度范围内，泼尼松的大分子结合不会饱和。
