Urinary metabolites of amitriptylinoxide and amitriptyline in single-dose experiments and during continuous therapy.
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.
Becher
B
B
Institut für Toxikologie, Universität Tübingen, Federal Republic of Germany.
Fischer
W
W
Taneri
Z
Z
Scholz
E
E
Müller
W E
WE
Breyer-Pfaff
U
U
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
D000639:Amitriptyline; C006566:amitriptyline N-oxide