Yamashita S K, Ludwig E A, Middleton E, Jusko W J
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo 14260.
Clin Pharmacol Ther. 1991 May;49(5):558-70. doi: 10.1038/clpt.1991.66.
The effects of ketoconazole on the pharmacokinetics and pharmacodynamics of intravenous prednisolone (14.8 mg) were assessed in six healthy volunteers. Subjects were studied with and without receiving ketoconazole, 200 mg orally for 6 days. The addition of ketoconazole did not significantly change the clearance (96 +/- 11 versus 90 +/- 11 ml/hr/kg), mean residence time (4.29 +/- 0.43 versus 4.45 +/- 0.59 hours), volume of distribution (0.41 +/- 0.02 versus 0.40 +/- 0.02 L/kg), or plasma protein binding characteristics of prednisolone. The suppressive effects of prednisolone on serum cortisol, blood basophil, and helper T lymphocyte values, assessed by the ratio of the area under the curve (AUC) after prednisolone administration to the baseline AUC, was not altered significantly by ketoconazole. The 50% inhibitory concentration values derived from pharmacodynamic models developed to describe the direct suppressive effects of corticosteroids indicated no alteration in intrinsic sensitivity in the presence of ketoconazole. Ketoconazole does not appear to alter the pharmacokinetics or the pharmacodynamic response patterns of selected direct suppression effects of single low doses of prednisolone.
在六名健康志愿者中评估了酮康唑对静脉注射泼尼松龙（14.8毫克）的药代动力学和药效学的影响。受试者在接受和未接受酮康唑（口服200毫克，共6天）的情况下进行研究。添加酮康唑并未显著改变泼尼松龙的清除率（96±11对90±11毫升/小时/千克）、平均驻留时间（4.29±0.43对4.45±0.59小时）、分布容积（0.41±0.02对0.40±0.02升/千克）或血浆蛋白结合特性。通过泼尼松龙给药后曲线下面积（AUC）与基线AUC的比值评估，酮康唑对泼尼松龙对血清皮质醇、血液嗜碱性粒细胞和辅助性T淋巴细胞值的抑制作用未显著改变。从用于描述皮质类固醇直接抑制作用的药效学模型得出的50%抑制浓度值表明，在存在酮康唑的情况下内在敏感性未改变。酮康唑似乎不会改变单次低剂量泼尼松龙的药代动力学或所选直接抑制作用的药效学反应模式。
