摘要：Propofol (2,6-diisopropylphenol), widely used an intravenous anesthetic, is rapidly metabolized to its glucuronide in the in vivo studies. Kinetic parameters for the glucuronidation of propofol and its analogs, such as 2,5-diisopropylphenol, 2- tert -butyl-6-methylphenol, 2- tert -butyl-5-methylphenol, 2,6-dimethylphenol and 2,5-dimethylphenol, were determined in vitro using human and rat liver microsomes. 2,5-Dimethylphenol and 2- tert -butyl-6-methylphenol exhibited the highest and lowest glucuronidation rates, respectively. Substitutes at the 2,6-positions gave lower glucuronidation rates than those at the 2,5-positions in both the human and rat microsomes. 2,5-Diisopropylphenol was glucuronidated at a lower rate in human than propofol. The affinity of uridine 5′-diphosphate (UDP)-glucuronosyltransferase for disubstituted phenols, such as propofol, 2,5-diisopropylphenol, 2,5-dimethylphenol, and 2- tert -butyl-6-methylphenol, gave higher K m values in human liver microsomes than in rat ones, and lower V max values showed similar relationship, expect for V max in propofol. The alkyl group at the 6 position showed a higher K m for glucuronidation by a steric hindrance in the human and rat microsomes. Our results propose that the glucuronidation of propofol and its analogs may not be explained by only a steric hindrance.
