Effects of Propofol Analogs on Glucuronidation of Propofol, an Anesthetic Drug, by Human Liver Microsomes
INTRODUCTION
UDP-glucuronosyltransferases (UGTs) catalyze the glucuronidation of a broad spectrum of endobiotic and xenobiotic substrates . In general, the resulting glucuronides are more hydrophilic, facilitating renal and biliary excretion. In addition to hepatic metabolism, high rates of gastrointestinal glucuronidation in rats and humans have been observed . Propofol (2,6-diisopropylphenol) is administered as a bolus for the induction of anesthesia and as an infusion for maintenance of anesthesia or for sedation. A rapid and complete recovery is a major advantage of this drug, which is attributable to extensive biotransformation of the parent compound. Propofol is suggested to be a substrate for one of the UGT isoforms, UGT1A9 [6,7]. There is a hypothesis that propofol could be orally used with a suitable inhibitor among analogs for preventing its rapid glucuronidation [8]. In order to seek for a suitable inhibitor of propofol biotransformation, we investigated the interactions between propofol and its analogs in the glucuronidation by recombinant human...