Influence of Phenobarbital Induction on the Stereoselectivity of Propranolol Glucuronidation in Rat Hepatic Microsome

Objective:To compare the glucuronidation stereoselectivities of propranolol in rat hepatic microsome and study the influence of inducer PB on the glucuronidation of propranolol enantiomers.Methods:Rat hepatic microsome from control and PB induced rats were prepared for glucuronidation reaction.A RP HPLC method was used to determine propranolol concentrations in microsome incubations.Results:Stereoselectivities were observed in enzymatic affinity(Km),maximum reaction speed(Vmax) and intrinsic clearance (Clint).PB induction singnificantly increased Vmax and Clint of R(+) propranolol( P 0.01 or 0.001),and Km and Vmax of S(-)propranolol( P 0.001);but Clint of S(-) propranolol was significantly lowed( P 0.05).The glucuronidation of propranolol in rat hepatic microsome has stereoselectivity of S(-) propranolol,and the induction of PB reduced the difference between R(+) and S(-) propranolol glucuronidation in rat hepatic microsome.Conclusion:The PB induction changed the catalysis abilities of rat hepatic microsome to propranolol glucuronidation and still remained the stereoselectivity of S(-) propranolol.