Species difference of site-selective glucuronidation of morphine

J Pharmacobiodyn. 1991 Apr;14(4):187-93. doi: 10.1248/bpb1978.14.187.


Species difference in glucuronidation of morphine was studied using mice, rats, guinea pigs and rabbits in vivo and in vitro. Morphine-3-glucuronide (M-3-G) and morphine-6-glucuronide (M-6-G) were determined by high-performance liquid chromatography. M-3-G was the major urinary metabolite of morphine in all these animal species. However, a remarkable species difference was observed in the urinary excretion of the M-6-G. Excretion ratios of the M-3-G to M-6-G were approximately 4:1 and 50:1 in guinea pigs and rabbits, respectively. The urinary excretion of M-6-G in mice and rats was too small to be determined. On the other hand, the ratios of uridine diphosphate-glucuronyltransferase (UDPGT) activities toward 3- and 6-hydroxyl groups of morphine in liver microsomes of mice, rats, guinea pigs and rabbits were approximately 300:1, 90:1, 4:1 and 40:1, respectively. Ratios of two morphine UDPGT activities in the liver microsomes of guinea pigs and rabbits, thus, reflected those of urinary excretion of morphine glucuronides.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biotransformation
  • Biphenyl Compounds / metabolism
  • Chromatography, High Pressure Liquid
  • Glucuronates / metabolism*
  • Glucuronosyltransferase / metabolism
  • Guinea Pigs
  • In Vitro Techniques
  • Liver / enzymology
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred Strains
  • Microsomes, Liver / enzymology
  • Morphine / metabolism*
  • Morphine Derivatives / metabolism
  • Nitrophenols / metabolism
  • Rabbits
  • Rats
  • Rats, Inbred Strains
  • Species Specificity


  • Biphenyl Compounds
  • Glucuronates
  • Morphine Derivatives
  • Nitrophenols
  • morphine-6-glucuronide
  • Morphine
  • 4-phenylphenol
  • Glucuronosyltransferase
  • morphine-3-glucuronide
  • 4-nitrophenol