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.
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
C K
CK
Kuo
N
N
Hanioka
Y
Y
Hoshikawa
K
K
Oguri
H
H
Yoshimura
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