Glucuronidation of propofol and its analogs by human and rat liver microsomes

Biol Pharm Bull. 2003 Feb;26(2):216-9. doi: 10.1248/bpb.26.216.


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 Km values in human liver microsomes than in rat ones, and lower Vmax values showed similar relationship, expect for Vmax in propofol. The alkyl group at the 6 position showed a higher Km 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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Glucuronides / chemistry
  • Glucuronides / pharmacokinetics*
  • Humans
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism*
  • Propofol / analogs & derivatives*
  • Propofol / pharmacokinetics*
  • Rats
  • Rats, Wistar


  • Glucuronides
  • Propofol