Pharmacokinetics of heptastigmine in rats.
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 tissues (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 in plasma and, to a lesser extent, in liver and kidney.
Segre
G
G
Institute of Pharmacology, Laboratory of Pharmacokinetics, University of Siena, Italy.
Cerretani
D
D
Baldi
A
A
Urso
R
R
D000284:Administration, Oral; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D010830:Physostigmine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D002800:Cholinesterase Inhibitors; C052450:physostigmine heptyl; D010830:Physostigmine