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Objective To study the pharmacokinetic characteristics of clobazam tablet in Chinese healthy subjects and evaluate the bioequivalence of test preparation(T)and reference preparation(R)under fasting or fed conditions.Methods A randomized,open-label,single-dose,two-period,two-way crossover bioequivalence trial was performed.34 healthy subjects were enrolled in fasting study and 30 in fed study.Each subjects received a single dose of T 20 mg or R 20 mg with a washout period of 28 days.Plasma concentrations of clobazam and its active metabolite,N-desmethylclobazam were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS).The pharmacokinetic parameters of clobazam and N-desmethylclobazam were calculated by non-compartment model.Geometric mean values for the T/R ratios of clobazam's main pharmacokinetic parameters and their corresponding 90 percent confidence intervals(CI)were evaluated to assess bioequivalence of the two preparations.Results In fasting study,the 90 percent CI of the geometric mean values for the T/R ratios were 94.46 to 103.82 percent for Cmax,99.64 to 103.62 percent for AUC0-tand 99.39 to 103.51 percent for AUC0-∞,respectively.In fed study,the 90 percent CI of the geometric mean values for the T/R ratios of were 93.86 to 106.02 percent for Cmax,100.37 to 104.51 percent for AUC0-tand 100.71 to 104.63 percent for AUC0-∞,respectively.Conclusion In this study,the 90 percent CI of the geometric mean values of Cmax,AUC0-tand AUC0-∞ for T/R ratios were all within the acceptable bioequivalence limits of 80 to 125 percent for clobazam.Therefore two formulations were considered bioequivalent.
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Objective To explore the effect of oridonin on the endoplasmic reticulum stress (ERS) in colonic epithelium of ulcerative colitis (UC) mice.Methods The UC mice model was established by sodium dextran sulfate (DSS),and the intervention group of oridonin and sulfasalazine was set up,the disease activity index (DAD was measured,the colonic tissue was evaluated by histopathologidscore (HPS),and RT-qPCR was used to detect the expression of inflammatory cytokines tumor factor-α (TNF-α),interleukin 6 (IL-6),cyclooxygenase 2 (COX-2),glucose-regulated protein 78 (GRP78),transcription factor EBP homologous protein (CHOP),activator transcription factor 6 (ATF6),protein kinase R like endoplasmic reticulum kinase (PERK) and inositol requiring enzyme 1α (IRE1α).Results The expression of TNF-α,IL-6,COX-2,GRP78,ATF6,CHOP,PERK and IRE1α mRNA in the colonic epithelium of the model group were all up-regulated obviously as compared with the healthy control group(P＜0.05,P＜0.01).When compared with the model group,DAI and HPS in oridonin-treated group were significantly decreased (P＜0.05,P＜0.01),which the curative effect was similar to that of the sulfasalazine group(P＞0.05,P＜0.01).The expression of TNF-α,IL-6,COX-2,GRP78,CHOP,ATF6 and PERK mRNA levels were significantly reduced in oridonin-treated group(P＜ 0.05,P＜0.01).Conclusion Oridonin can alleviate colonic inflammation induced by DSS and its mechanism may be related to ERS of colonic epithelial tissue.
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@#Functionalized graphene oxide is prepared based on graphene. It has attracted great interest from all over the world due to its good solubility, biocompatibility, high loading rate, and easy modification. This paper summarizes the surface modification of graphene oxide, and its applications on anti-tumor, antibacteria, anti-hypertension, gene therapy and biosafety as a drug carrier, providing new methods and ideas in the biomedical field.