title: Urinary metabolites of amitriptylinoxide and amitriptyline in single-dose experiments and during continuous therapy.
abstract: In a cross-over design, six healthy volunteers received 50 mg amitriptylinoxide (AT-NO) IV and orally and 50 mg amitriptyline (AT) IV. Urine was collected completely for 8 h and occasionally up to 48 h. In addition, five patients each under treatment with AT-NO or AT for tension headache collected 24-h urine samples. The following compounds were analysed by HPLC: AT-NO, E- and Z-10-hydroxy-AT-NO (E- and Z-10-OH-AT-NO), free and conjugated AT, E- and Z-10-OH-AT and their mono- and didemethylated analogues, and 2-OH-nortriptyline (2-OH-NT). Unchanged AT-NO in urine accounted for an average of 34% and 22% of the single IV and oral doses, respectively, and for 28% in continuous therapy, with a further 8-9% being excreted as E- and Z-10-OH-AT-NO. The remaining part was converted to the same metabolites as was AT. In the steady state the measured compounds accounted for 74% and 77% of the daily AT-NO and AT doses, respectively. The renal plasma clearance of AT-NO varied between 75 and 265 ml/min in the six volunteers. Tubular secretion must play an important part in the renal excretion of AT-NO.
authors.affiliation: Institut für Toxikologie, Universität Tübingen, Federal Republic of Germany.
authors.forename: B
authors.initials: B
authors.lastname: Becher
authors.forename: W
authors.initials: W
authors.lastname: Fischer
authors.forename: Z
authors.initials: Z
authors.lastname: Taneri
authors.forename: E
authors.initials: E
authors.lastname: Scholz
authors.forename: W E
authors.initials: WE
authors.lastname: Müller
authors.forename: U
authors.initials: U
authors.lastname: Breyer-Pfaff
mesh_terms: D000328:Adult; D000639:Amitriptyline / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000652:urine*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006261:Headache / Q000188:drug therapy; D006801:Humans; D008297:Male
chemical_list: D000639:Amitriptyline; C006566:amitriptyline N-oxide