Effects of microsome enzyme induced by phenobarbarbital on the stereoselectivity of recemic propranolol glucuronidation metabolism

Objective: To study the stereoselectivity of R-(+) and S-(-)-propranololglucuronidation and metabolic interaction between R(+)- and S-(-)-propranolol. Methods: A RP-HPLC analytical method was developed for determination of R-(+)- and S-(-)-propranolol glucuronide (PG) incubated with rat hepatic microsome induced with phenobarbital (PB). The method was applied to investigate the stereoselectivity metabolism of racemic propranolol glucuronidation in vitro. Results: In control and PB group,the concentration of R-(+)-PG produced at different substrates was higher than that of S-(-)-PG. Compared with the control,the V max and Cl int for R(+)- and S-(-)-propranolol increased significantly;the K m for R(+)-propranolol was elevated,while that for S-(-) propranolol was decreased. Conclusion: There is a stereoselectivity in glucuronidation of propranolol in rat hepatic microsome induced with PB and R-(+)-propranolol is preferred. Metabolic interaction between R-(+)- and S-(-)-propranolol exists with a concentration-dependent mode.