Effects of microsome enzyme induced by phenobarbarbital on the stereoselectivity of recemic propranolol glucuronidation metabolism.
- Author:
Lian-Jun LUAN
1
;
Qing SHAO
;
Xiao-Hong ZHANG
;
Su ZENG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Enzyme Induction; Microsomes, Liver; enzymology; Phenobarbital; pharmacology; Propranolol; analogs & derivatives; metabolism; Rats; Rats, Sprague-Dawley; Stereoisomerism
- From: Journal of Zhejiang University. Medical sciences 2004;33(1):7-10
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the stereoselectivity of R-(+) and S-(-)-propranolol glucuronidation and metabolic interaction between R(+)- and S-(-)-propranolol.
METHODSA 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.
RESULTIn 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.
CONCLUSIONThere 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.
