Rost K L, Brockmöller J, Weber W, Roots I
Institute of Clinical Pharmacology, Klinikum Steglitz Free University of Berlin, Germany.
Clin Pharmacol Ther. 1991 Aug;50(2):141-9. doi: 10.1038/clpt.1991.118.
Ganglioside GM1 multiple-dose pharmacokinetics were investigated in five healthy male volunteers. Doses of 100 mg were administered either intravenously or intramuscularly for 21 days, and the washout was followed-up for a further 21 days. The highly specific binding of the beta-subunit of cholera toxin was used to quantify ganglioside GM1 levels in plasma, urine, and feces. This dose regime increased the ganglioside GM1 steady-state plasma levels two to three orders of magnitude above the endogenous levels of 0.132 mg/L (coefficient of variation, 8.9%). Large and variable amounts of ganglioside GM1 were found in feces before and during treatment without relation to the dosage. No ganglioside GM1 could be detected in urine at any time. Plasma kinetics were linear with a biexponential disposition. Exogenously administered ganglioside GM1 was confined mainly to the blood volume as indicated by a steady-state volume of distribution of 6.98 +/- 3.57 L and appears to be excreted mainly in the form of metabolites. The total clearance was very slow at 1.61 +/- 0.37 ml/min. Absorption after intramuscular administration was slow (time to reach maximum concentration greater than 12 hours) and yielded steady-state concentrations somewhat lower compared with the intravenous infusion.
在五名健康男性志愿者中研究了神经节苷脂GM1的多剂量药代动力学。以100毫克的剂量静脉注射或肌肉注射给药，持续21天，并在之后的21天进行洗脱期随访。利用霍乱毒素β亚基的高特异性结合来定量血浆、尿液和粪便中的神经节苷脂GM1水平。这种给药方案使神经节苷脂GM1的稳态血浆水平比内源性水平0.132毫克/升（变异系数为8.9%）高出两到三个数量级。在治疗前和治疗期间，粪便中发现大量且变化不定的神经节苷脂GM1，与剂量无关。在任何时候尿液中均未检测到神经节苷脂GM1。血浆动力学呈线性，具有双指数分布。外源性给予的神经节苷脂GM1主要局限于血容量，稳态分布容积为6.98±3.57升，似乎主要以代谢产物的形式排泄。总清除率非常缓慢，为1.61±0.37毫升/分钟。肌肉注射后的吸收缓慢（达到最大浓度的时间大于12小时），与静脉输注相比，稳态浓度略低。
