Kong A N, Jungbluth G L, Pasko M T, Beam T R, Jusko W J
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo 14260.
Pharmacotherapy. 1990;10(1):29-34.
The pharmacokinetics of methylprednisolone sodium succinate (MPHS) and methylprednisolone (MP) were determined in six patients undergoing open heart surgery with cardiopulmonary bypass. Plasma concentrations of both compounds were measured by high-performance liquid chromatography after doses of MPHS of 1.7-2.4 g. The prodrug ester MPHS yields MP with an average formation rate constant of 0.70 +/- 0.29 hr-1. Peak concentrations of MP occur around 1-2 hours after loading and additional administration of MPHS. The pharmacokinetic values of the two drugs in patients having cardiopulmonary bypass were compared to those in younger, healthy subjects. The volume of distribution of MPHS was lower in the patients, and that of MP was similar to the value in controls. Total clearances of both agents were reduced by about 5 and 2 times. The elimination half-life of MPHS was increased slightly, whereas that of MP increased more than twice in the patients. Significant alterations in clearances occurred in patients, but concentrations of MP were appreciable and prolonged MP due to the extensive formation of MP from MPHS and reduced clearance of MP.
在六名接受体外循环心脏直视手术的患者中测定了琥珀酸甲泼尼龙（MPHS）和甲泼尼龙（MP）的药代动力学。给予1.7 - 2.4 g MPHS后，通过高效液相色谱法测量两种化合物的血浆浓度。前药酯MPHS生成MP的平均生成速率常数为0.70±0.29小时⁻¹。负荷及额外给予MPHS后，MP的峰值浓度在1 - 2小时左右出现。将接受体外循环的患者中这两种药物的药代动力学值与年轻健康受试者的进行了比较。患者中MPHS的分布容积较低，而MP的分布容积与对照组的值相似。两种药物的总清除率分别降低了约5倍和2倍。MPHS的消除半衰期略有增加，而患者中MP的消除半衰期增加了两倍多。患者的清除率发生了显著改变，但由于MPHS大量生成MP以及MP清除率降低，MP的浓度较高且持续时间延长。
