Urinary excretion of conjugates of dothiepin and northiaden (mono-N-demethyl-dothiepin) after an oral dose of dothiepin to humans

Eur J Drug Metab Pharmacokinet. Jan-Mar 1986;11(1):29-32. doi: 10.1007/BF03189772.

Abstract

Only small amounts of unconjugated dothiepin (unchanged drug) and northiaden were excreted in urine over a 72 hr period. More than 10% of the dose was excreted as conjugated dothiepin and less than 0.8% of the dose as conjugated northiaden. Conjugated dothiepin was thus found to be an important metabolite of dothiepin. Conjugated dothiepin and northiaden were hydrolyzed with beta-glucuronidase, and their hydrolysis inhibited with 1,4 saccharolactone. Conjugated dothiepin and northiaden were found to be a quaternary ammonium-linked glucuronide and a tertiary N-glucuronide, respectively.

MeSH terms

  • Adult
  • Biotransformation
  • Dibenzothiepins / metabolism*
  • Dothiepin / analogs & derivatives
  • Dothiepin / metabolism*
  • Dothiepin / urine
  • Glucaric Acid / analogs & derivatives
  • Glucaric Acid / pharmacology
  • Glucuronidase / antagonists & inhibitors
  • Humans
  • Hydrolysis
  • Male
  • Middle Aged

Substances

  • Dibenzothiepins
  • northiaden
  • saccharolactone
  • Glucuronidase
  • Glucaric Acid
  • Dothiepin