Plasma and brain pharmacokinetics of amitriptyline and its demethylated and hydroxylated metabolites after one and six half-life repeated administrations to rats.
The purposes of the present study were as follows: 1. After an acute intraperitoneal (IP) administration of amitriptyline (AMI) to male Sprague-Dawley rats we found that: (i) its absorption rate is rapid; (ii) its elimination half-life is much shorter than in humans; and (iii) its levels largely exceeded those of its metabolites. The most important metabolites being 10-hydroxynortriptyline and nortriptyline in plasma and brain, respectively. 2. After six (every half-life) repeated IP administrations: (i) AMI kinetic parameters were unchanged; and (ii) amounts of metabolites were significantly increased and the levels of AMI were lowered both in plasma and brain.
Coudore
F
F
Laboratoire de Pharmacologie, Equipe NPPUA (NeuroPsychoPharmacologie-Université d'Auvergne, Clermont-Ferrand, France.
Besson
A
A
Eschalier
A
A
Lavarenne
J
J
Fialip
J
J
D000639:Amitriptyline / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D006207:Half-Life; D008297:Male; D009661:Nortriptyline / Q000031:analogs & derivatives / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
D000929:Antidepressive Agents, Tricyclic; C013567:10-hydroxynortriptyline; D000639:Amitriptyline; D009661:Nortriptyline