Multiple-dose pharmacokinetics of ganglioside GM1 after intravenous and intramuscular administration to healthy volunteers

Abstract

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.

Novel Therapeutic Approach for the Treatment of Alzheimer's Disease by Peripheral Administration of Agents with an Affinity to β-Amyloid

“…2 D). Plasma GM1 has also been shown to be maintained above the endogenous GM1 level for several days after cessation of administration once steady-state levels have been achieved (Rost et al, 1991). We therefore included a 1 week washout period for the GM1 study.…”

Phenotypic drug discovery: a case for thymosin alpha-1

“…In a pharmacokinetics study in lung cancer, the subjects in the loading dose treatment arm showed similar results as above. Plasma levels returned to basal levels within 24 h of administration and there was no evidence of accumulation ( 75 , 76 ).…”

Thymosin α1 and Its Role in Viral Infectious Diseases: The Mechanism and Clinical Application

“…Solid-phase synthesis is the only technique approved for the clinical production of Tα1. Tα1 is commonly provided twice a week through subcutaneous injection, with a conventional dosage range of 0.8-6.4 mg and a multi-dose range of 1.6-16 mg [26]. A pharmacokinetic study showed that after subcutaneous injection, Tα1 is well-absorbed in the body, and its peak blood drug concentration (Cmax, the highest blood drug concentration after administration) is reached at 1-2 h, with a plasma half-life (t1/2, an estimate of the time it takes for the concentration or amount in the body Furthermore, electrostatic interactions may enhance the binding of Tα1 to hyaluronic acid (HA) and interfere with the binding of HA to CD44 and the motor receptor RHAMM, inhibiting viral infection progression [24].…”