AIM: To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride(SM

以SDS阴离子表面活性剂作流动相,酸性、中性及两性药物为受试药物,运用三相平衡理论考察影响阴离子型胶束液相色谱（AMLC）溶质保留行为的几个因素。保留由溶质与胶束相及修饰后固定相的综合作用决定。有机调节剂正丙醇的加入改变了溶质从水相到固定相或到胶束相的平衡,保留取决于溶质疏水性和静电性间的平衡。此外对羟基苯甲酸酯类同系物的亲脂性与3种细菌最小抑菌浓度具有显著相关性,提示其抑菌机理主要取决于药物与生物膜的亲和性。

生物膜为液晶态磷脂双分子层结构，其中蛋白质镶嵌在生物膜上，处于脂质环境中，因此药物膜的转运、药物接近膜中蛋白质以及随后结合过程等均与药物和生物膜间的相互作用有着密切联系。药物的膜/水分配系数（Km）是评价药物与生物膜间相互作用的定量参数，为药物与生物膜间各种分子作用力的总和，包括静电、氢键和疏水等作用力及立体效应等[1，2]。药物与生物膜间相互作用的评价系统一直是研究中的热点。最初正辛醇/水系统为模型分配系统，但是由于其不是理想的生物膜模拟相，因此不能用来准确描述药物与生物膜间的相互作用。最近出现的磷脂膜色谱可较好地模拟细胞膜有序磷脂层的空间环境，因此在评价药物与生物膜间的相互作用、预测药物跨膜转运以及生物活性上均明显优越于正辛醇/水系统[3]。虽然我们已证明这两个系统在亲脂性测量尺度上存在明显差别，但是并没有说明溶质与两个生物膜模拟相的相互作用机制的差别[4]。本文考察了温度对溶质分子在这两个分配系统中分配的影响，并从溶质分配过程中的熵变和焓变的角度对这两个分配系统进行了比较。

A marked difference in the dissolution rate between two brands of nimodipine tablets was observed using a newly developed dissolution medium of pH 4.5 acetate buffer containing 0.05% sodium dodecyl sulfate (SDS).However,when pH 4.5 acetate buffer containing 0.3% SDS was used as dissolution medium, which was specified in the British Pharmacopoeia(BP)2000 edition,the dissolution results of the both brands conformed to the BP requirements and no significant difference in dissolution was observed.The dissolution data obtained for two commercial brands of nimodipine tablets indicate the superiority of the proposed system as a discriminatory dissolution medium for nimodipine tablets.The relative bioavailability of the two brands of nimodipine tablets was determined in healthy adult volunteers after a single dose in a randomized crossover study. Plasma concentrations were determined by a liquid chromatography-tandem mass spectrometry method. Statistical comparison of the AUC0-T, AUC0–∞, Cmax, and Tmax indicated a significant difference in the two brands of nimodipine tablets.

The purpose of this study was to investigate the distribution of Grepafloxacin (GPFX),a new quinolone antimicrobial agent, in the lung epithelial lining fluid(ELF)and the alveolar macrophage(AM)in rats,which are potential infection sites in respiratory tract infections.We also aimed to clarify the mechanism governing the transferability of GPFX into the alveolus compartment from a kinetic point of view.The AUC ratios of ELFWplasma and AMWplasma after the oral administration of GPFX were 5.69

This study was performed to characterize the protonation equilibrium at the molecular level and pH-dependent lipophilicity of olamufloxacin.The deprotonation fraction of the carboxyl group as a function of pH was specifically calculated at the critical wavelength 294 nm,where UV pH-dependent absorbance of olamufloxacin was independent of the ionized state of the aminopyrrolidinyl amino group but heavily depended on that of the carboxyl moiety.Accordingly,micro-protonation equilibrium could be described using a nonlinear leastsquares regression program MULTI.In contrast,macro-protonation equilibrium was depicted at most wavelengths where olamufloxacin absorbance was influenced by ionized states of both proton-binding groups,results coinciding with the former.Furthermore,distribution features of four microspecies in aqueous phase were assessed. The apparent partition coefficient versus pH profile of olamufloxacin showed a parabolic curve in n-octanol/buffer system which reached peak near pH8,agreeing with the above determined isoelectric point(pI).Ion-pair effect was observed for olamufloxacin under an acidic condition, eliciting experimental values higher than those theoretically calculated,which was similar to ciprofloxacin but not levofloxacin due to amino group type.Moreover,olamufloxacin was moderately lipophilic in comparison with other quinolones,with an apparent partition coefficient of 1.95 at pH7.4.

It has been shown that transport(s)are involved in the uptake of estradiol 17 glucuronide (E217βG) by the choroid plexus(CP).The purpose of this study is to compare the substrate specificity of the transporter in the CP with those of rat organic anion transporting polypeptide 1 (rOatp1) and rOatp3.Methods. The expression of rOatp1 and rOatp3 in rat CP was confirmed by RT-PCR and Western blot analyses. The substrate specificity of rOatp1 and rOatp3 was compared using cDNA-transfected LLC-PK1 cells. The uptake of E217 G by rat isolated CP was determined by centrifugal filtration technique.Results. PCR analyses demonstrated that the mRNA expression of rOatp3 was abundant in the CP, whereas that of rOatp1 was low.Immunohistochemical staining revealed that rOatp3 is expressed on the apical membrane of the CP. Kinetic parameters (Km and Ki values)of rOatp3 were similar to those for rOatp1. The results of mutual inhibition study suggest that E217βG and taurocholate share the same mechanism in the CP. Corticosterone, estrone-3-sulfate and indomethacin are moderate inhibitors, but no effects by digoxin, paminohippurate,benzylpenicillin and cimetidine were observed.Conclusions. rOatp3 is most possible candidate transporter involved in the uptake of organic anions on the brush border membrane of the choroid epithelial cells.