PLASMA AND BRAIN PHARMACOKINETICS OF AMITRIPTYLINE AND ITS DEMETHYLATED AND HYDROXYLATED METABOLITES AFTER ONE AND 6 HALF-LIFE REPEATED ADMINISTRATIONS TO RATS

The purposes of the present study were as follows: 1. After an acute i ntraperitoneal (IP) administration of amitriptyline (AMI) to male Spra gue-Dawley rats we found that: (i) its absorbtion rate is rapid; (ii) its elimination half life is muck shorter than in humans; and (iii) it s 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 a dministrations: (i) AMI kinetic parameters were unchanged; and (ii) am ounts of metabolites were significantly increased and the levels of AM I were lowered both in plasma and brain.