Pharmacokinetics of amitriptyline and its demethylated and hydroxylated metabolites in streptozocin-induced diabetic rats.
Plasma and brain levels of amitriptyline (AMI), its demethylated and hydroxylated metabolites were determined after acute IP administration of AMI (20 mg/kg) in streptozocin-induced diabetic Sprague-Dawley rats. Results showed 1. in plasma: rapid AMI absorption, but slow elimination; the proportion of AMI similar to those of the rest of compounds; the proportion of its demethylated metabolite, nortriptyline, 1.8-fold higher than that of 10-hydroxy-nortriptyline. 2. in brain: the proportions of AMI and nortriptyline were 9.5- and 2.6-fold higher respectively, than those of whole hydroxylated metabolites, which represented 7.4% of the total amount.
Coudoré
F
F
Laboratoire de Pharmacologie, Faculté de Pharmacie, Faculté de Médecine, Université d'Auvergne, Clermont-Ferrand, France.
Besson
A
A
Courteix
C
C
Eschalier
A
A
Lavarenne
J
J
Fialip
J
J
D000639:Amitriptyline / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000493:pharmacokinetics*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006900:Hydroxylation; D007274:Injections, Intraperitoneal; D008297:Male; D009661:Nortriptyline / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D000929:Antidepressive Agents, Tricyclic; C013567:10-hydroxynortriptyline; D000639:Amitriptyline; D009661:Nortriptyline