Möllmann H, Hochhaus G, Rohatagi S, Barth J, Derendorf H
Medical Clinic Bergmannsheil, University of Bochum, Germany.
Pharm Res. 1995 Jul;12(7):1096-100. doi: 10.1023/a:1016287104656.
The pharmacokinetics and pharmacodynamics of deflazacort after oral administration (30 mg) to healthy volunteers were determined and compared with those of 20 mg of methylprednisolone and 25 mg of prednisolone.
Methylprednisolone, prednisolone and the active metabolite of deflazacort, 21-desacetyldeflazacort, were measured in plasma using HPLC. For the assessment of pharmacodynamics, differential white blood cell counts were obtained over 24 hours. An integrated pharmacokinetic-pharmacodynamic (PK-PD) model was applied to link corticosteroid concentrations to the effect on lymphocytes and granulocytes.
Deflazacort is an inactive prodrug which is converted rapidly to the active metabolite 21-desacetyldeflazacort. Maximum concentrations of 21-desacetyldeflazacort averaged 116 ng/ml and were observed after 1.3 h. The average area under the curve was 280 ng/ml.h, and the terminal half-life was 1.3 h. 21-Desacetyldeflazacort was cleared significantly faster than both methylprednisolone and prednisolone. The PK-PD-model was suitable to describe time course and magnitude of the observed effects. The results were consistent with reported values for glucocorticoid receptor binding affinities for the investigated compounds.
Due to the short pharmacokinetic half-life of its active metabolite, pharmacodynamic effects of deflazacort are of shorter duration than those of methylprednisolone and prednisolone. The PK-PD model allows good prediction of pharmacodynamic effects based on pharmacokinetic and receptor binding data.
测定健康志愿者口服30毫克去氟可特后的药代动力学和药效学，并与20毫克甲泼尼龙和25毫克泼尼松龙进行比较。
采用高效液相色谱法测定血浆中甲泼尼龙、泼尼松龙和去氟可特的活性代谢物21-去乙酰去氟可特。为评估药效学，在24小时内进行白细胞分类计数。应用整合药代动力学-药效学（PK-PD）模型将皮质类固醇浓度与对淋巴细胞和粒细胞的作用联系起来。
去氟可特是一种无活性的前体药物，可迅速转化为活性代谢物21-去乙酰去氟可特。21-去乙酰去氟可特的最大浓度平均为116纳克/毫升，在1.3小时后观察到。曲线下平均面积为280纳克/毫升·小时，终末半衰期为1.3小时。21-去乙酰去氟可特的清除速度明显快于甲泼尼龙和泼尼松龙。PK-PD模型适合描述观察到的效应的时间过程和强度。结果与所研究化合物的糖皮质激素受体结合亲和力的报告值一致。
由于其活性代谢物的药代动力学半衰期较短，去氟可特的药效学作用持续时间比甲泼尼龙和泼尼松龙短。PK-PD模型能够根据药代动力学和受体结合数据很好地预测药效学效应。
