Absorption, tissue distribution and excretion of radiolabelled compounds in rats after administration of [14C]-L-alpha-glycerylphosphorylcholine

Eur J Drug Metab Pharmacokinet. Apr-Jun 1993;18(2):173-80. doi: 10.1007/BF03188793.

Abstract

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 [14C]-glycerol ([14G]-GPC) or [14C]-choline ([14C]-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 gave a wide distribution of radioactivity, particularly concentrated in the liver, kidney, lung and spleen compared to blood. Brain concentrations of [14C]-GPC were comparable to ([14G]-GPC) or lower than ([14C]-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 in increasing amounts within 24 h of dosing. In all cases renal and fecal excretion of radioactivity was low and comparable for [14G]-GPC and [14C]-GPC. Mostly the administered radioactivity was exhaled as 14CO2, 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.

Publication types

  • Comparative Study

MeSH terms

  • Absorption
  • Administration, Oral
  • Animals
  • Blood-Brain Barrier / physiology
  • Brain / metabolism
  • Carbon Radioisotopes
  • Choline / pharmacokinetics
  • Female
  • Glycerol / pharmacokinetics
  • Glycerylphosphorylcholine / blood
  • Glycerylphosphorylcholine / pharmacokinetics*
  • Injections, Intravenous
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution

Substances

  • Carbon Radioisotopes
  • Glycerylphosphorylcholine
  • Choline
  • Glycerol