Study on the bioequivalence of gliclazide sustained released tablet in healthy volunteers / 中国药理学通报

Aim To evaluate the bioequivalence of two preparations of gliclazide in healthy volunteers.Methods The concentration of gliclazide was measured by high performance liquid chromatography(HPLC) after a single or multiple dosage of gliclazide sustained released tablet in healthy volunteers.The pharmacokinetic parameters of the two preparations were calculated by 3P97 program.LnAUC0~∞,lnAUC0~72 and lnAUC0~? were used to evaluate the bioequivalence of the two preparations with analysis of variance and two one-side t-test.Results Both the gliclazide extended action tablet were best fitted to one-compartment model.The main parameters of the tested and reference gliclazide after a single dose were as follows:Cmax(2.07?0.61) and(2.26?0.61)mg?L-1;Tmax(5.10?0.55)h and(5.05?0.51)h;T12Ka(1.50?0.26)h and(1.52?0.27)h;T12Ke(8.89?1.56)h and(8.68?1.72)h;MRT(22.63?1.01)h and(22.38?0.93)h;AUC0~72(39.19?8.03)mg?h-1?L-1 and(39.26?8.37)mg?h-1?L-1;AUC0~∞:(45.80?9.51)mg?h-1?L-1 and(45.57?9.76)mg?h-1?L-1;F0~72 and F0~∞(100.19?6.22)% and(100.85?5.88)%,respectively.The main parameters of the tested and reference gliclazide after multiple dose were as follows:Cmax(4.83?0.86)mg?L-1 and(4.69?0.64)mg?L-1;Cmin(0.68?0.14) mg?L-1 and(0.66?0.12)mg?L-1;Tmax:(4.10?0.45) h and(4.10?0.55)h;T12Ka:(2.03?0.53)h and(2.04?0.40)h;T12Ke:(7.24?0.87)h and(7.09?1.14)h;MRT(9.17?0.30)h and(9.19?0.37)h;AUCSS:(41.62?6.48) mg?h-1?L-1 and(42.18?6.03)mg?h-1?L-1;Cav:(1.73?0.27)mg?L-1 and(1.76?0.25)mg?L-1;DF(240.85%?34.07)and(230.23%?24.80%) respectively.The relative bioavailability was(98.60?4.60)%.The AUC0~T,AUC0~∞ or AUCSS,Cmax and Tmax were bioequivalent between the two preparations.Conclusion The tested and reference gliclazide sustained released tablet are bioequivalent.

Regulating effect of oxymatrine on TGF-?1 in CCl_4-induced hepatic fibrosis rats / 中国药理学通报

Aim To explore the anti-fibrotic effect of Oxymatrine(OM) on CCl4-induced liver fibrosis in rats and its modulation on the TGF-?1.Methods A hepatic fibrosis model was induced by CCl4.The levels of Alanine transaminase(ALT),aspartic transaminase(AST),type-Ⅰ collagen and TGF-?1 in plasma were detected by chemical Kit.The deposition of collagen was observed with H&E and Masson staining.Pathological changes were observed under light microscope in 8 randomly selected fields in each group.RT-PCR method was applied to detect the expression of TGF-?1 mRNA in hepatic tissue.Results The concentration of serum ALT,AST,type-Ⅰ collagen and TGF-?1 was significantly reduced in the middle and high dose treated groups compared with that of model group.A significant reduction of collagen deposition and rearrangement in OM-treated group was displayed in histopathological changes.The expression of TGF-?1 mRNA was considerably decreased in the treated animals.Conclusions Oxymatrine is effective in reducing the production and deposition of collagen in the liver tissue of experimental groups,and it has an obvious protective effect on model rats.It may be one of the therapeutic mechanisms to modulate the expression of TGF-?1 mRNA.