[Pharmacokinetics of n-(5-oxynicotinoyl)-L-glutamic acid calcium salt upon bolus administration in rats and rabbits: interspecies extrapolation]

Eksp Klin Farmakol. 2010 Dec;73(12):31-5.
[Article in Russian]

Abstract

The pharmacokinetics of N-(5-oxynicotinoyl)-L-glutamate (ONG) was studied in rats (doses, 20, 100 and 500 mg/kg) and rabbits (50 mg/kg) after bolus administration of calcium salt of N-(5-oxynicotinoyl)-L-glutamic acid (Ampasse preparation). The ONG concentration in the blood serum was determined by HPLC assay with fluorimetric detection. The lower limit of accurate detection for ONG was 100 ng/ml. The ONG pharmacokinetics in rats was linear at relatively small doses (20-100 mg/kg) but nonlinear at a large dose (500 mg/kg). The ONG concentration decay had a two-phase character in both rats and rabbits, so that the pharmacokinetic profiles were fitted to a biexponential equation of the two-compartment model. Systemic pharmacokinetic parameters determined in rats and rabbits, respectively, were as follows: total clearance, 18 and 15 ml/(min kg); steady state distribution volume, 330 and 880 ml/kg; mean retention time, 0.3 and 1.0 h; half-life, 0.73 and 2.3 h. Using the allometric approach to the interspecies extrapolation of the pharmacokinetic data, the half-life of ONG in humans is predicted to be 4 h.

MeSH terms

  • Animals
  • Glutamates / pharmacokinetics*
  • Glutamates / pharmacology
  • Male
  • Neuroprotective Agents / pharmacokinetics*
  • Neuroprotective Agents / pharmacology
  • Nicotinic Acids / pharmacokinetics*
  • Nicotinic Acids / pharmacology
  • Nootropic Agents / pharmacokinetics*
  • Nootropic Agents / pharmacology
  • Rabbits
  • Rats
  • Rats, Wistar
  • Species Specificity

Substances

  • Glutamates
  • Neuroprotective Agents
  • Nicotinic Acids
  • Nootropic Agents
  • nooglutil