Comparison of the disposition and of the metabolic pattern of Reboxetine, a new antidepressant, in the rat, dog, monkey and man.
The purpose of this study was to compare the disposition and the metabolic pattern of Reboxetine in several species, including man. [14C]-Reboxetine was given orally to the rat, the dog, the monkey (5 mg/kg) and man (2 and 4 mg/kg). Radioactivity was eliminated both by the renal and faecal route in the rat and the dog, mainly in urine in the monkey and man. Reboxetine was extensively metabolized. A number of urinary metabolites were quantified by radio-HPLC and tentatively identified by comparison with the retention times of reference compounds. Suggested routes of metabolic transformation are: 2-O-dealkylation; hydroxylation of the ethoxyphenoxy ring; oxidation of the morpholine ring; morpholine ring-opening; and combinations of these. Metabolites were partially or completely conjugated with glucuronic acid and/or sulphuric acid.
Cocchiara
G
G
Farmitalia Carlo Erba R&D, Erbamont Group, Milan, Italy.
Battaglia
R
R
Pevarello
P
P
Strolin Benedetti
M
M
D000284:Administration, Oral; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003640:Dealkylation; D004285:Dogs / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D008252:Macaca fascicularis / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains / Q000378:metabolism; D000077593:Reboxetine
D000928:Antidepressive Agents; D009025:Morpholines; D000077593:Reboxetine