Effects of microsome enzyme induced by phenobarbarbital on the stereoselectivity of recemic propranolol glucuronidation metabolism / 浙江大学学报·医学版

ABSTRACT

<p><b>OBJECTIVE</b>To study the stereoselectivity of R-(+) and S-(-)-propranolol glucuronidation and metabolic interaction between R(+)- and S-(-)-propranolol.</p><p><b>METHODS</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>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.</p>