Urinary metabolites of amitriptylinoxide and amitriptyline in single-dose experiments and during continuous therapy

Psychopharmacology (Berl). 1992;106(3):303-10. doi: 10.1007/BF02245409.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amitriptyline / analogs & derivatives*
  • Amitriptyline / pharmacokinetics
  • Amitriptyline / therapeutic use
  • Amitriptyline / urine*
  • Biotransformation
  • Chromatography, High Pressure Liquid
  • Female
  • Headache / drug therapy
  • Humans
  • Male

Substances

  • Amitriptyline
  • amitriptyline N-oxide