Urinary excretion of conjugates of dothiepin and northiaden (mono-N-demethyl-dothiepin) after an oral dose of dothiepin to humans.
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.
D000328:Adult; D001711:Biotransformation; D003988:Dibenzothiepins / Q000378:metabolism*; D004308:Dothiepin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D005937:Glucaric Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005966:Glucuronidase / Q000037:antagonists & inhibitors; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008875:Middle Aged
D003988:Dibenzothiepins; C030224:northiaden; C009194:saccharolactone; D005966:Glucuronidase; D005937:Glucaric Acid; D004308:Dothiepin