title: Minor and clinically non-significant interaction between toloxatone and amitriptyline.
abstract: The possibility of a pharmacokinetic interaction between amitriptyline and toloxatone (a new MAOI-A) has been studied in 17 depressed in-patients. Amitriptyline and its demethylated and hydroxylated metabolites in blood and urine were measured at steady state after the administration of amitriptyline with and without toloxatone in steady state. The metabolic status of patients was determined using the dextromethorphan phenotyping test. There was only a minor pharmacokinetic interaction between amitriptyline (AMT) and toloxatone, with a small increase in the AMT/NT (nortriptyline) plasma ratio: 0.68 before and 0.78 after toloxatone. The urinary excretion and plasma levels of AMT and its metabolites were not affected by the co-therapy. Three of the patients were poor metabolisers, but this did not predict the magnitude of the drug interaction. The interaction does not justify plasma level monitoring of amitriptyline as the change in pharmacokinetics was so small.
authors.affiliation: Laboratoire de Pharmacologie Clinique, CHU de Besançon, France.
authors.forename: S
authors.initials: S
authors.lastname: Vandel
authors.forename: G
authors.initials: G
authors.lastname: Bertschy
authors.forename: M C
authors.initials: MC
authors.lastname: Perault
authors.forename: M
authors.initials: M
authors.lastname: Sandoz
authors.forename: S
authors.initials: S
authors.lastname: Bouquet
authors.forename: R
authors.initials: R
authors.lastname: Chakroun
authors.forename: S
authors.initials: S
authors.lastname: Guibert
authors.forename: B
authors.initials: B
authors.lastname: Vandel
mesh_terms: D000328:Adult; D000368:Aged; D000639:Amitriptyline / Q000493:pharmacokinetics*; D003863:Depression / Q000188:drug therapy / Q000378:metabolism; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000493:pharmacokinetics*; D010080:Oxazoles / Q000493:pharmacokinetics*; D023303:Oxazolidinones; D010641:Phenotype; D015203:Reproducibility of Results
chemical_list: D008996:Monoamine Oxidase Inhibitors; D010080:Oxazoles; D023303:Oxazolidinones; D000639:Amitriptyline; C010798:toloxatone