Kawahara K, Awaji T, Uda K, Sakai Y, Hashimoto Y
Eur J Drug Metab Pharmacokinet. 1986 Jan-Mar;11(1):29-32. doi: 10.1007/BF03189772.
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.
在72小时内，尿液中仅排出少量未结合的多塞平（未变化的药物）和去甲替林。超过10%的剂量以结合型多塞平的形式排出，而以结合型去甲替林形式排出的剂量不到0.8%。因此，结合型多塞平被发现是多塞平的一种重要代谢产物。结合型多塞平和去甲替林用β-葡萄糖醛酸苷酶水解，其水解作用被1,4-内酯抑制。结合型多塞平和去甲替林分别被发现是季铵连接的葡萄糖醛酸苷和叔N-葡萄糖醛酸苷。
