Chen M F, Shimada F, Kato H, Yano S, Kanaoka M
First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
Endocrinol Jpn. 1990 Jun;37(3):331-41. doi: 10.1507/endocrj1954.37.331.
We investigated the pharmacokinetics of prednisolone (PSL) in six healthy men, with or without glycyrrhizin (GL), to confirm whether GL influences the metabolism of PSL in humans. Each subject received an intravenous administration of 0.096 mg/kg of prednisolone hemisuccinate (PSL-HS, equivalent to 0.075 mg/kg of PSL), with or without 200 mg of GL. Blood samples were taken from a peripheral vein at 5, 10, 15, 30 and 45 min, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 h after PSL-HS infusion. The concentration of total PSL in the plasma was analyzed by high-performance liquid chromatography, and the free PSL was measured by an isocolloidosmolar equilibrium dialysis method. The pharmacokinetic parameters of PSL were determined, using noncompartmental analysis. GL was found to increase significantly the concentration of total PSL at 6, 8 h, and of free PSL at 4, 6, and 8 h after PSL-HS infusion. GL was also found to modify the pharmacokinetics of PSL. After the administration of GL, the area under the curve (AUC) increased, total plasma clearance (CL) decreased, and the mean residence time (MRT) was prolonged. However, only those of AUC, CL, and MRT of free PSL were significantly different. The volume of distribution at a steady-state (Vdss) of both total and free PSL showed no evident change. This suggests that GL increases the plasma PSL concentrations by inhibiting the metabolism of PSL and that it potentiates pharmacological effects of PSL.
我们研究了在六名健康男性中，有或没有甘草酸（GL）存在时泼尼松龙（PSL）的药代动力学，以确认GL是否会影响人体中PSL的代谢。每位受试者静脉注射0.096 mg/kg氢化泼尼松琥珀酸钠（PSL-HS，相当于0.075 mg/kg PSL），有或没有200 mg GL。在PSL-HS输注后5、10、15、30和45分钟以及1、1.5、2、3、4、6、8、10、12和24小时从外周静脉采集血样。通过高效液相色谱法分析血浆中总PSL的浓度，通过等胶体渗透压平衡透析法测量游离PSL。使用非房室分析确定PSL的药代动力学参数。发现GL在PSL-HS输注后6、8小时显著增加总PSL的浓度，在4、6和8小时显著增加游离PSL的浓度。还发现GL改变了PSL的药代动力学。给予GL后，曲线下面积（AUC）增加，总血浆清除率（CL）降低，平均驻留时间（MRT）延长。然而，只有游离PSL的AUC、CL和MRT有显著差异。总PSL和游离PSL在稳态时的分布容积（Vdss）均无明显变化。这表明GL通过抑制PSL的代谢增加血浆PSL浓度，并增强PSL的药理作用。
