Jusko W J, Milad M A, Ludwig E A, Lew K H, Kohli R K
Department of Pharmaceutics, State University of New York at Buffalo 14260, USA.
Clin Nephrol. 1995 Jan;43 Suppl 1:S16-9.
Methylprednisolone (MP) pharmacokinetics and its directly suppressive effects on cortisol secretion and cell trafficking were compared in 6 chronic renal failure (CRF) subjects and 6 healthy controls. After IV administration of MP 0.6 mg/kg as Solu-Medrol, the pharmacokinetics of methylprednisolone were similar. The clearance was about 280 ml/hr/kg, volume of distribution was 1.1 l/kg, t1/2 was 2.7 hr, and fraction unbound was 0.2. Physiologic pharmacodynamics models were applied for the suppression of cortisol secretion and recirculation of basophils, T-helper cells, and T-suppressor cells. The net response (area under the curve) and inhibitory concentrations (IC50) of methylprednisolone for each pharmacodynamic parameter were similar in both groups. As the pharmacokinetics of other corticosteroids are altered in CRF, the lack of pharmacokinetic/dynamic changes of methylprednisolone may offer a therapeutic advantage for CRF patients.
在6名慢性肾衰竭（CRF）受试者和6名健康对照者中比较了甲泼尼龙（MP）的药代动力学及其对皮质醇分泌和细胞转运的直接抑制作用。静脉注射0.6mg/kg甲泼尼龙，商品名为Solu-Medrol后，甲泼尼龙的药代动力学相似。清除率约为280ml/（小时·千克），分布容积为1.1l/kg，半衰期为2.7小时，未结合分数为0.2。应用生理药效学模型来抑制皮质醇分泌以及嗜碱性粒细胞、辅助性T细胞和抑制性T细胞的再循环。两组中甲泼尼龙对每个药效学参数的净反应（曲线下面积）和抑制浓度（IC50）相似。由于其他皮质类固醇的药代动力学在CRF中会发生改变，甲泼尼龙药代动力学/药效学无变化可能为CRF患者提供治疗优势。
