AIM:To study the influence of Inducers of drug metabolismenzyme,β-naphthoflavone(BNF)and dexamethasone(DEX),on the stereoselective metabolism of propafenone inthe rat hepatic microsomes.METHODS:Phase I metabolism of propafenone was studiedusing the microsomes induced by BNF and DEX and thenon-induced microsome was used as the control.Theenzymatic kinatics parameters of propafenone enantiomerswere calculated by regress analysis of Eadie-Hofstee Plots.Propafenone enantiomer concentrations were assayed by achiral HPLC.RESULTS:The metabolite of propafenone,N-desalkylpropafenone,was found after incubation ofpropafenone with the rat hepatic microsomes induced byBNF and DEX.In these two groups,the stereoselectivityfavoring R(-)Isomer was observed in metabolism at lowsubstrate concentrations of racemic propafenone,but lostthe atereoselectivity at high substrate concentrations.However,in control group,no stereoselectivity wasobserved.The enzyme kinetic parameters were:①K_m.Control group:R(-) 83±6,S(+)94±7;BNF group:R(-)105±6,S(+)128±14;DEX group:R(-) 86±11,S(+) 118±16;② U_(max).Control group:R(-)0.75±0.16,S(+)0.72±0.07;BNF group:R(-)1.04±0.15,S(+)1.07±14;DEX group:R(-)0.93±0.06,S(+)1.04±0.09;③Cl_(Int).Control group:R(-)8.9±1.1,S(+)7.6±0.7;BNFgroup:R(-)9.9±0.9,S(+)8.3±0.7;DEX group:R(-)10.9±0.8,S(+) 8.9±0.9.The enantiomeric differences inKm arid Cl_(Int) were both significant,but not in U_(max),in BNFand DEX group.Whereas enantlornedc differencas in threeparameters were all insignificant in control group.Furthermore,K_m and U_(max) were both significantly less thanthose in BNF or DEX group.In the rat liver microsomeInduced by DEX,nimodipine(NDP)decreased thestereoselectivity in propafenone metabolism at low substrateconcentration.The inhibition of NDP on the metabolism ofpropafenone was stereoselective with R(-)-isomer beingimpaired more than S(+)-isomer.The inhibition constant(Ki)of S(+)-and R(-)-propafenone,calculated fromDixon plots,was 15.4 and 8.6 mg.L~(-1),respectively.CONCLUSION:CYP1 A subfamily(induced by BNF)and CYP3A4(induced by DEX)have pronounced contribution topropafenone N-desalkyiation which exhibitedstereoselectivity depending on substrate concentration.Themolecular base for this phenomenon is the stereoselectivityin affinity of substrate to the enzyme activity centers insteadof at the catalyzing sites. AIM: To study the influence of Inducers of drug metabolismenzyme, β-naphthoflavone (BNF) and dexamethasone (DEX), on the stereoselective metabolism of propafenone inthe rat hepatic microsomes. METHODS: Phase I metabolism of propafenone was studied using the microsomes induced by BNF and DEX and thenon-induced microsome was used as the control. The enzymatic kinatics parameters of propafenone enantiomers were calculated by regress analysis of Eadie-Hofstee Plots. Propafenone enantiomer concentrations were assayed by achiral HPLC .RESULTS: The metabolite of propafenone, N-desalkylpropafenone, was found after incubation of propafenone with the hepatic hepatic microsomes induced by BNF and DEX. These two groups, the stereoselectivity of RF (-) Isomer was observed in metabolism at lowsubstrate concentrations of racemic propafenone, but lost the aterelectivity at high substrate concentrations. Despite, in control group, no stereoselectivity wasobserved. enzyme kinetic parameters were: ① K_m.Control group: R (-) 83 ± 6, S (+) 94 ± 7, BNF group: R (-) 105 ± 6, S (+) 128 ± 14; DEX group: R (-) 86 ± 11, S (+) 118 ± 16; ② U max max: Control group: R ± 0.75 ± 0.16, S ± 0.72 ± 0.07; BNF group: R ± 1.04 ± 0.15, S ± 1.07 ± 14; DEX group: R (- ) (0.93 ± 0.06, S (+) 1.04 ± 0.09); ③Cl_ (Int) .Control group: R ± 8.9 ± 1.1, S ± 7.6 ± 0.7; BNFgroup: R ± 9.9 ± 0.9, S + ) 8.3 ± 0.7; DEX group: R (-) 10.9 ± 0.8, S (+) 8.9 ± 0.9. The enantiomeric differences inKm arid Cl_ (Int) were both significant but not in U max, in BNF and DEX group. Whereas enantlornedc differencas in three pararameters were all insignificant in control group. Still further, Km and Umax (both) were both significantly less thanthose in BNF or DEX group. In the rat liver microsome led by DEX, nimodipine (NDP) decreased the severity of propafenone metabolism at low substrateconcentration.The inhibition of NDP on the metabolism ofpropafenone was stereoselective with R (-) - isomer beingimpaired more than S (+) - isomer. inhibition of NDP on S (+) - and R (-) - propafenone, calculated fromDixon plots, was 15.4 and 8. 6 mg.L -1, respectively.CONCLUSION: CYP1 A subfamily (induced by BNF) and CYP3A4 (induced by DEX) have pronounced contribution topropafenone N-desalkyiation which rendered stereoselectivity on on substrate concentration .molecular base for this phenomenon is the stereoselectivity of affinity of substrate to the enzyme activity centers instead of at the catalyzing sites.