Pharmacokinetics of heptastigmine in rats

• Published in: Pharmacological research 1992-02, Vol.25 (2), p.139-146
• Main Authors: Segre, G., Cerretani, D., Baldi, A., Urso, R.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Biological and medical sciences; Cholinesterase Inhibitors - pharmacokinetics; hepastigmine; Injections, Intramuscular; Injections, Intravenous; Male; Medical sciences; Neuropharmacology; pharmacokinetics; Pharmacology. Drug treatments; Physostigmine - administration & dosage; Physostigmine - analogs & derivatives; Physostigmine - blood; Physostigmine - pharmacokinetics; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Inbred Strains; Tissue Distribution
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/1043-6618(92)91382-Q

Heptastigmine is a new long acting cholinesterase inhibitor that affects behaviour in a number of cognitive tests in animals. We have studied its pharmacokinetics in rats: plasma kinetics were evaluated after single intravenous dose (2 mg/kg), intramuscular (4 mg/kg) and oral (4 and 8 mg/kg) administration. Tissue distribution (heart, liver, kidney and brain) was studied after single intramuscular (4 mg/kg) and oral (8 mg/kg) administration. Plasma and tissue kinetics were also investigated after repeated oral doses (8 mg/kg b.i.d. for 7 days). Heptastigmine levels in plasma and tissues were determined using an HPLC method with an electrochemical detector. After a single dose, heptastigmine remained for a long time in plasma (the terminal half-life was about 12 h), distributed widely in tissue (the volume of distribution was about 61) and brain concentrations were very high (4–22 times those found in plasma). After repeated oral doses, the drug levels increased plasma and, to a lesser extent, in liver and kidney.