Stereoselective propranolol metabolism in two drug induced rat hepatic microsomes

作     者：Li X Zeng S 

作者机构：College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310031China 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2000年第6卷第1期

页      面：74-78页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：the National Natural Science Foundation of China No.39370805 

主　　题：Subject headings propranolol enantiomers rat hepatic microsome phenobarbital β-naphthoflavone 

摘      要：AIM To study the influence of inducers BNFand PB on the stereoselective metabolism ofpropranolol in rat hepatic *** Phase Ⅰ metabolism of propranololwas studied by using the microsomes induced byBNF and PB and the non-induced microsome asthe *** enzymatic kinetic parameters ofpropranolol enantiomers were calculated byregression analysis of Lineweaver-Burk *** concentrations were assayed *** A RP-HPLC method was developed todetermine propranolol concentration in rathepatic *** linearity equations forR（+）-propranolol and S（-）-propranolol wereA=705.7C+311.2C（R = 0.9987）and A= 697.2C+311.4C（R = 0.9970）*** each enantiomer were 98.9%,99.5%,101.0%at 60 μmol/L,120 μmol/L,240 μmol/*** the concentration level of120 μmol/L,propranolol enantiomers weremetabolized at different rates in *** concentration ratio R（+）/S（-）of control and PB induced microsomesincreased with time,whereas that of microsomeinduced by BNF *** assayed enzymeparameters were:*** group:R（+）30+8,S（-）18+5;BNFgroup:R（+）34+3,S（-）39±7;PB group:R（+）38±17,S（-）36±*** group:R（+）1.5+0.2,S（-）2.9±0.3;BNF group:R（+）3.8±0.3,S（-）3.3±0.5;PB group:R（+）0.07±0.03,S（-）1.94±*** group:R（+）60±3,S（-）170±30;BNF group:R（+）111.0±1,S（-）84± 5;PBgroup:R（+）2.0±2,S（-）56.0±*** compared with unpaired ttests showed that no stereoselectivity wasobserved in enzymatic affinity of threemicrosomes to enantiomers and their catalyticabilities were quite different and *** with the control,microsome induced by BNF enhanced enzymeactivity to propranolol R（+）-enantiomer,andmicrosome induced by PB showed less enzymeactivity to propranolol S（-）-enantiomer whichremains the same stereoselectivities as that ofthe *** Enzyme activity centers of themicrosome were changed in composition andregioselectivity after the in