Effects of propofol analogs on glucuronidation of propofol, an anesthetic drug, by human liver microsomes.
To prevent rapid forming O-glucuronide of propofol (2,6-diisopropylphenol), an intravenous anesthetic, effects of propofol analogs were investigated. Propofol was predominately glucuronidated by human UGT1A9 and intestinal or liver microsomes. 2,5-Diisopropylphenol inhibited the propofol glucuronidation. A possibility of developing orally administrable agents or of reducing propofol dose by coadministration is suggested.
Shimizu
Makiko
M
Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
Matsumoto
Yoshiaki
Y
Yamazaki
Hiroshi
H
D018686:Anesthetics, Intravenous / Q000378:metabolism*; D000818:Animals; D004347:Drug Interactions; D020719:Glucuronides / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007313:Insecta / Q000201:enzymology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000201:enzymology; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D015742:Propofol / Q000031:analogs & derivatives / Q000378:metabolism*; D051381:Rats; D013045:Species Specificity; D000090264:UDP-Glucuronosyltransferase 1A9
D018686:Anesthetics, Intravenous; D020719:Glucuronides; C000715591:UGT1A9 protein, human; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9; D015742:Propofol