Multiple‐dose pharmacokinetics of ganglioside GM 1 after intravenous and intramuscular administration to healthy volunteers

Ganglioside GM 1 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 β‐subunit of cholera toxin was used to quantify ganglioside GM 1 levels in plasma, urine, and feces. This dose regime increased the ganglioside GM 1 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 GM 1 were found in feces before and during treatment without relation to the dosage. No ganglioside GM 1 could be detected in urine at any time. Plasma kinetics were linear with a biexponential disposition. Exogenously administered ganglioside GM 1 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 >12 hours) and yielded steady‐state concentrations somewhat lower compared with the intravenous infusion. Clinical Pharmacology and Therapeutics (1991) 50, 141–149; doi: 10.1038/clpt.1991.118