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

Summary

The kinetics and metabolism ofl-α-glycerylphosphoryl-choline (α-GPC) were investigated in male and female rats after i.v. (10 mg/kg) and oral doses (100–300 mg/kg). α-GPC was labelled with [14C]-glycerol ([14C]-GPC) or [14C]-choline ([14C]-GPC). Different kinetic and metabolic profiles were observed after i.v. and oral administration. It is assumed that α-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 as14CO2, 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.

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References

  1. 1.

    Canal N., Franceschi M., Alberoni M., Castiglioni C., De Moliner P., Longoni A. (1991): Effect ofl-α-glycerylphosphorylcholine on amnesia caused by acopolamina. Int. J. Clin. Pharm. Ther. Tox., 29, 103–107.

    CAS  Google Scholar 

  2. 2.

    Spano P.F., Trabucchi M. (1990): α-GFC (Colina alfoscerato) un farmaco ad azione integrata sulle funzioni neuronali. Stato dell’arte. Basi Razionali Ter., (in Italian), 20, 1–93.

    Google Scholar 

  3. 3.

    Trabucchi M., Govoni S., Battaini F. (1986): Changes in interaction between CNS cholinergic and dopaminergic neurons induced byl-α-glycerylphosphorylcholine, a cholinomimetic drug. II Farmaco, 4, 323–334.

    Google Scholar 

  4. 4.

    Lopez C.M., Govoni S., Battaini F., et al. (1991): Effect of a new cognition enhancer alpha-glycerylphosphorylcholine, on acopolamine induced amnesia and brain acetylcholine. Pharmacol. Biochem. Behav., In press.

  5. 5.

    Baldwin J.J., Cormotzer W.E. (1968): Rat kidney glycerylphosphorylcholine diesterase. Biochim. Biophys. Acta, 164, 199–204.

    Google Scholar 

  6. 6.

    Dawson R.M.C. (1956): Liver’s glycerylphosphorylcholine diesterase. Biochem. J., 62, 689–693.

    CAS  PubMed  Google Scholar 

  7. 7.

    Webster G.R., Marples A.E., Thompson R.H.S. (1957): Activity of glycerylphosphorylcholine diesterase in nervous tissues. Biochem. J., 65, 374–377.

    CAS  PubMed  Google Scholar 

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Correspondence to G. Abbiati.

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Abbiati, G., Fossati, T., Lachmann, G. et al. Absorption, tissue distribution and excretion of radiolabelled compounds in rats after administration of [14C]-l-α-glycerylphosphorylcholine. Eur. J. Drug Metab. Pharmacokinet. 18, 173–180 (1993). https://doi.org/10.1007/BF03188793

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Keywords

  • [14C]-l-α-Glycerylphosphorylcholine
  • disposition and metabolism
  • rat