Formation of a quaternary N-glucuronide of amitriptyline in human liver microsomes

Pharmacol Toxicol. 1987 Nov;61(5):342-6. doi: 10.1111/j.1600-0773.1987.tb01832.x.


Amitriptyline N-glucuronide was isolated from urine of a patient treated with therapeutic doses of amitriptyline. The glucuronide was hydrolyzed by hot alkaline treatment and, to a lesser degree, by treatment with beta-glucuronidase. A method for the direct measurement of amitriptyline glucuronide by HPLC was developed. Human liver microsomes were shown to glucuronidate amitriptyline in the presence of UDPGA, and the activity varied 7-fold among microsomes from 13 different human livers. The glucuronidation of amitriptyline was inhibited by p-nitrophenol but not by morphine. E-10-hydroxynortriptyline, a major metabolite of amitriptyline, had only a slight inhibitory effect on the glucuronidation of amitriptyline. No significant correlation was found between the glucuronidation of amitriptyline and that of E-10-hydroxynortriptyline in the microsomes studied.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amitriptyline / metabolism*
  • Chromatography, High Pressure Liquid
  • Glucuronates / metabolism
  • Humans
  • In Vitro Techniques
  • Microsomes, Liver / enzymology
  • Microsomes, Liver / metabolism*
  • Spectrophotometry, Ultraviolet


  • Glucuronates
  • Amitriptyline