Pharmacokinetic studies of cholinesterase inhibitors.
The pharmacokinetic of some centrally acting cholinesterase inhibitors that have been used to improve memory in patients with dementia of Alzheimer's type, was compared. The original compound in this class, physostigmine has an elimination half-life of 20-30 min. Galanthamine, tacrine and the metabolite 1-hydroxytacrine (velnacrine) have longer elimination half-lives of 1.6-6 hours mainly due to a larger volume of distribution. The concentration of tacrine in the cerebrospinal fluid (CSF) was less than the average plasma concentration in the dosing interval; a ratio of 0.74. The concentration of 1-hydroxytacrine and other metabolites of tacrine in the CSF were higher than the average concentrations of the compounds in plasma.
Johansson
M
M
Medical Product Agency, Uppsala, Sweden.
Nordberg
A
A
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005702:Galantamine / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010830:Physostigmine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013619:Tacrine / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000627:therapeutic use
D005702:Galantamine; D013619:Tacrine; D010830:Physostigmine