TY - JOUR T1 - The Glucuronidation of Morphine by Dog Liver Microsomes: Identification of Morphine-6-<em>O</em>-Glucuronide JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 661 LP - 663 VL - 28 IS - 6 AU - Christopher King AU - Bernita Finley AU - Ronald Franklin Y1 - 2000/06/01 UR - http://dmd.aspetjournals.org/content/28/6/661.abstract N2 - Canines are used extensively in the pharmaceutical industry for the preclinical screening of novel therapeutics, yet comparatively little is known about the phase 2 metabolism in this species. In humans, morphine is known to undergo extensive metabolism by glucuronidation, and the UDP-glucuronosyltransferase isoform, which catalyzes the formation of morphine-3-O-glucuronide and morphine-6-O-glucuronide is UGT2B7. This study was designed to investigate the glucuronidation of morphine using dog liver microsomes. Liver microsomes from beagle dogs catalyzed the glucuronidation of morphine-3(and 6)-O-glucuronide at rates 4 to 10 times that of rhesus monkey and human liver microsomes. The Km of morphine using beagle dog liver microsomes was ∼270 μM, which is similar to that found for expressed human UGT2B7. The Vmax for morphine, using dog liver microsomes, was 27 nmol/min/mg of protein. Flunitrazepam inhibited the glucuronidation of morphine in dog liver microsomes, and the Ki was 40 μM, which is similar to human UGT2B7 for other substrates. The effects of detergents were also investigated with dog liver microsomes, and Brij 35 and Brij 58 were found to be the best detergents to use for maximal activation of the dog liver morphine UGT. These studies suggest that dog has a UGT2B isoform similar to human UGT2B7. The American Society for Pharmacology and Experimental Therapeutics ER -