Derendorf H, Möllmann H, Krieg M, Tunn S, Möllmann C, Barth J, Röthig H J
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville 32610.
Pharm Res. 1991 Feb;8(2):263-8. doi: 10.1023/a:1015864709082.
The pharmacokinetics and pharmacodynamics of methylprednisolone were investigated after intravenous administration of methylprednisolone phosphate to healthy subjects at seven different doses (16 to 1000 mg). Forty different pharmacodynamic parameters were followed for 1 week. The pharmacodynamic data were analyzed as a function of time as well as cumulative effects in form of the areas under the effect-time curves. Statistically significant dose-dependent effects of methylprednisolone were observed for 15 pharmacodynamic parameters. Highly significant (P less than or equal to 0.0001) effects were increases in glucose levels, number of white blood cells, and segmented granulocytes as well as a decrease in the number of lymphocytes. For these pharmacodynamic effects an integrated pharmacokinetic/pharmacodynamic model was derived that translates the methylprednisolone plasma concentration-time profiles into effect-time profiles. This model allows prediction of pharmacodynamic effects for any single dose in the range studied at any time point.
在7个不同剂量（16至1000毫克）下，对健康受试者静脉注射磷酸甲泼尼龙后，研究了甲泼尼龙的药代动力学和药效学。跟踪40个不同的药效学参数长达1周。药效学数据作为时间以及效应-时间曲线下面积形式的累积效应的函数进行分析。观察到15个药效学参数存在甲泼尼龙的剂量依赖性显著效应。血糖水平、白细胞数量和分叶粒细胞数量增加以及淋巴细胞数量减少具有高度显著（P≤0.0001）的效应。针对这些药效学效应，推导了一个综合药代动力学/药效学模型，该模型将甲泼尼龙血浆浓度-时间曲线转化为效应-时间曲线。该模型能够预测在所研究范围内任何时间点任何单剂量的药效学效应。
