Species difference of site-selective glucuronidation of morphine.
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.
Kuo
C K
CK
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Hanioka
N
N
Hoshikawa
Y
Y
Oguri
K
K
Yoshimura
H
H
D000818:Animals; D001711:Biotransformation; D001713:Biphenyl Compounds / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005965:Glucuronates / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000201:enzymology; D009020:Morphine / Q000378:metabolism*; D009022:Morphine Derivatives / Q000378:metabolism; D009596:Nitrophenols / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D001713:Biphenyl Compounds; D005965:Glucuronates; D009022:Morphine Derivatives; D009596:Nitrophenols; C035349:morphine-6-glucuronide; D009020:Morphine; C019046:4-phenylphenol; D014453:Glucuronosyltransferase; C018108:morphine-3-glucuronide; C024836:4-nitrophenol