ABSORPTION, TISSUE DISTRIBUTION AND EXCRETION OF RADIOLABELED COMPOUNDS IN RATS AFTER ADMINISTRATION OF [C-14] L-ALPHA-GLYCERYLPHOSPHORYLCHOLINE

The kinetics and metabolism of L-alpha-glycerylphosphoryl-choline (alpha-GPC) were investigated in male and female rats after i.v. (10 mg/kg) and oral doses (100-300 mg/kg). Alpha-GPC was labelled with [C-14]-glycerol ([14G]-GPC) or [C-14]-choline [C-14]-choline ([C-14]-GPC). Different kinetic and metabolic profiles were observed after i.v. and oral administration. It is assumed that alpha-GPC is hydrolyzed by phosphodiesterases in the gut mucosa. The different labelled metabolites have different kinetic properties of absorption, distribution and clearance, leading to different blood concentration-time curves of total radioactivity. Both labelled compounds save a wide distribution of radioactivity, particularly concentrated in the liver, kidney, lung and spleen compared to blood. Brain concentrations of [C-14]-GPC were comparable to ([14G]-GPC) or lower than ([C-14]-GPC) total blood radioactivity. The metabolite profile in the perfused brain showed a small amount of choline and two unknown metabolites, probably the same as in blood. In addition, choline was incorporated into brain phospholipids increasing amounts within 24 h of dosing. In all caws renal and fecal excretion of radioactivity was low and comparable for [14G]-GPC and [C-14]-GPC. Mostly the administered radioactivity was exhaled as (CO2)-C-14, this degradation being faster and more pronounced for the glycerol-labelled metabolites than for the choline-labelled metabolites for both routes of administration. In all cases the results were the same for male and female rats.