Drug Liposome Partitioning as a Tool for the Prediction of Human Passive Intestinal Absorption

Purpose. Appropriate physicochemical parameters are desired for the prediction of passive intestinal drug absorption during lead compound selection and drug development. Methods. Liposome distribution coefficients measured titrimetrically and solubility data at pH 6.8 were used to characterize 21 structurally diverse ionizable drugs covering a range from <5% to almost complete absorption. Results. A sigmoidal relationship was found between the percentage of human passive intestinal absorption and a new absorption potential parameter calculated from liposome distribution data and the solubility dose ratio. In contrast, the human absorption data did not correlate with an octanol-based absorption potential or partitioning data alone. Poor correlations were found between liposome and octanol partitioning of ionic species or nonionic bases indicating the profound differences of the partitioning systems. Conclusions. Liposome distribution coefficients of ionizable drugs derived by a pH-metric titration were successfully used to calculate a parameter that correlates with the percentage of passive intestinal absorption in humans. Profound differences between liposome and octanol partitioning were found for a highly diverse set of species. This titration technique may serve to generate liposome partitioning data for the selection and optimization of lead compounds and in drug development.     

Partition Behaviour of Drugs in Microemulsions Measured by Electrokinetic Chromatography

Pharmaceutical Research -     

湖南省12家医院1996年心血管类国家基本药物的用药分析

根据国家制定的基本药物目录，就湖南省12家医院1996年心血管类药物的购入情况进行分析，了解到心血管类药物的使用信息，讨论了制定国家基本药物的合理性。随着医药水平的发展，国家基本药物目录有必要进行定期调整，以引导临床心血管类药物的合理使用。     

Interaction of Polyethyleneglycol-Phospholipid Conjugates with Cholesterol-Phosphatidylcholine Mixtures: Sterically Stabilized Liposome Formulations

Purpose. The purpose of this study was to investigate polyethyleneglycol (PEG)-phosphatidylethanolamine (PE) conjugate interaction with cholesterol-phospholipid mixtures in an attempt to explain the effect of cholesterol on liposome circulation time. Methods. Differential scanning calorimetry, NMR, electron microscopy, dynamic light scattering and fluorescence spectroscopy were the major methods used. Results. Studies performed in the absence of cholesterol indicated the formation of three distinct physical states depending on the chain length of PEG in PEG-PE. Mixed micelle formation was observed at concentrations of PEG( 1,000)-DPPE above 7 mol% of lipid. Phase separated lamellae were observed at all concentrations of PEG( 12,000)-DPPE (Bedu-Addo et al. Pharm. Res. 13:710–717 (1996)). Upon incorporation of high concentrations of cholesterol >30 mol% into the lipid bilayer, the formation of phase separated lamellae was completely inhibited and the formation of mixed micelles significantly reduced. At high concentrations of PEG( 1,000)-PE, solubilization of the bilayer occurred with preferential solubilization of cholesterol over phosphati-dylcholine. Maximum steric stabilization (surface protection) was observed with low concentrations of short chain PEG-PE and high concentrations of cholesterol. Conclusions. The study provides a physical mechanism for the following observations: the blood circulation time is significantly increased or decreased with liposomes highly enriched with cholesterol or PEG-PE respectively.     

Relationships in the Structure–Tissue Distribution of Basic Drugs in the Rabbit

The relationship between the tissue-to-plasma partition coefficients (K _p) and drug lipophilicity was investigated using highly lipophilic drugs with apparent partition coefficients of 150 or above in an octanol–water system at pH 7.4. Ten clinically popular basic drugs with different dissociation coefficients (pK _a) and lipophilicity were used. The K _p values were determined in nondisposing organs after the i.v. administration of individual drugs in rabbits. The free fraction in plasma and the blood-to-plasma concentration ratio were determined in vitro. Then the tissue-to-plasma ratios of nonionized and unbound drug concentrations (K _pfu) were calculated from K _pf (ratio of unbound drug). The true octanol–water partition coefficient of the nonionized drugs (P) was used to analyze the K _pf and K _pfu. In all tissues, log K _pfu was more highly correlated with log P than log K _pf.     

某些廉价国家基本药物供应不足的原因及对策分析

目的 为解决某些廉价基本药物供应不足问题提出建议.方法 通过查阅、分析文献,结合廉价基本药物短缺现状,分析其原因,提出解决办法.结果 某些廉价基本药物由于利润过低、储备和信息披露机制不完善,以及产业链的不稳定等原因,造成短缺现象.结论 解决某些廉价国家基本药物供应不足问题可以从几个方面入手：采用邀请招标和限高保低的招标定价方式,完善国家药品储备制度,明确国家基本药物供应保障的行政管理责任机构,加强医药产业政策引导.     

抗精神病药对血脂影响的临床分析

目的比较抗精神病药对精神分裂症患者血脂的影响,评价药物的安全性。方法选择260例精神分裂症患者,临床分为奥氮平组（61例）,喹硫平组（65例）,利培酮组（72例）,阿立哌唑组（62例）,药物治疗8周前后TC（胆固醇）、TG（甘油三脂）、HDLC（高密度脂蛋白）、LOLC（低密度脂蛋白）、载脂蛋白A、载脂蛋白B。结果阿立哌唑对血脂影响较小,差异无统计学意义（P〉0．05）。其他三种抗精神病药物可引起血脂TC、TG、LOL．C、apoB升高,其中TC、TG升高明显,其升高程度由强到弱依次为：奥氮平〉喹硫平〉利培酮,差异均有统计学意义（P〈0．05或P〈0．01）;可引起血脂HDL水平降低,其降低程度由强到弱依次为：奥氮平〉喹硫平〉利培酮,差异均有统计学意义（P〈0．05）。结论四种抗精神病药物中阿立哌唑对血脂影响较小,奥氮平、喹硫平、利培酮皆引起血脂异常,在治疗精神分裂症时应采取相应的干预措施。     

高效液相色谱法同时测定5种抗乙肝药物的研究

目的建立高效液相色谱法同时测定五种抗乙肝药物。方法采用水-乙腈-三氟乙酸在Waters Xbridge C 18柱(4.6×250mm,5μm)上进行梯度洗脱,流速为1.0mL·min^-1,检测波长为260nm,柱温35℃。结果5种药物在35min内均能达到基线分离,线性范围良好,相关系数均大于0.999;平均回收率n=3为99.4~101.7%(RSD:0.1~1.7%),精密度和稳定性试验的RSD分别为0.6%~0.8%,0.4%~0.5%,检测限0.1~0.2μg·mL^-1。在恩替卡韦制剂样品中检出假阳性样品,检出物为阿德福韦酯。结论该方法适用于五种抗乙肝药物同时测定,并且能准确筛查出高仿假药。     

1996年湖南省12家医院国家基本药物抗感染药用药分析

本文对湖南地区12家医院1996年抗感染药购入数据进行统计．并参照国家基本药物目录．按金额排序法列出购入金额前50位的药品。对数据进行分析和预测。以供国家基本药物目录修正．医院内部基本药物目录连选参考．指导临床合理用药。     

1996～1997年我院抗肿瘤类国家基本药物的使用分析及趋势预测

本文对我院1996年1月～1997年12月2年间抗肿瘤药使用数据进行统计，按照金额排序法歹l］出销售金额排在前70位的抗肿瘤药物，并参照国家基本药物目录，了解到我院抗肿瘤类国家基本药物的使用比例为70％左右。通过对数据进行分析和预测，认识到国家基本药物目录应随着医药科技的发展而进行必要的调整，从而指导临床合理用药。     

国内离子色谱技术在化学药品质控中的应用

摘 要离子色谱技术因其分离机制独特,可弥补液相色谱或气相色谱对离子型药物分析时的不足,使其在药品检测领域中的应用越来越广泛。本文综述了离子色谱技术以及国内近年来在化学药品质量控制中的应用。     

我院门诊部178例糖尿病患者路径干预后降糖药物使用情况观察

目的探讨在我院第三门诊部对糖尿病患者进行有效路径干预治疗后,分析门诊部2009～2011年降糖药物的使用情况,为降低糖尿病的并发症、急诊率、住院率,和提高糖尿病临床合理用药提供一些参考。方法采用金额排序法和DDD分析法,对我门诊部2009—2011年度降糖药的用药金额、糖尿病药品所占总药品金额的比例、用药频度（DDDs）、日均费用（DDC）等进行统计与分析。结果2009～2011年降糖药的品种、数量及销售金额等逐年增长;我门诊部用药金额前3位为阿卡波糖、30R胰岛素、那格列奈;用药频度前3位为阿卡波糖、30R胰岛素、格列齐特;日均费用前3位为30R胰岛素、R胰岛素、N胰岛素。结论对我门诊182例糖尿病患者建立观察病历,对178例糖尿病患者治疗前后进行对比,在对糖尿病患者有效路径干预后,降低了临床药占比例,节省了医疗资源。糖尿病干预前、后对比,糖尿病患者并发症、急诊率、住院率明显下降,两组之间差异有统计学意义。我门诊部降糖药路径干预后的应用较为合理。医生开具的处方能够从患者的病情需要出发,真正做到用药经济、安全、合理、有效。     

试析“医疗机构使用假、劣药”的法律适用

目的:为修订《药品管理法》中与医疗机构使用假、劣药有关的规定提供参考。方法:通过对《药品管理法》第四十八条和第四十九条第一款涉及到的相关法理知识以及《药品管理法》其他相关条款的分析,结合立法宗旨、立法本意对医疗机构使用假、劣药行为进行解析。结果与结论:《药品管理法》第四十八条和第四十九条第一款存在严重立法瑕疵,禁止生产销售假、劣药,而没有禁止医疗机构"使用",尽管《药品管理法实施条例》已做了补救,但还需要立法机关高度重视,在下一轮修订中予以完善。     

Binding of Basic Drugs to Rat Lung Mitochondria

The role of the mitochondria in the accumulation of basic amine drugs in the rat lung was studied. Drug binding to the mitochondria was rapid and reached maximum levels after 2.5 min of incubation. Lipophilic basic drugs accumulated in the mitochondria more than nonlipophilic basic drugs and non-basic drugs, and the accumulation was dose dependent. Schatchard plots revealed at least two independent sets of binding sites for basic drugs in the mitochondria. The binding was competitively inhibited by other basic drugs but not nonbasic drugs. The degree of inhibition by competing basic drugs was correlated with their lipid solubilities. These findings with isolated mitochondria agree with previous results obtained with the perfused lung preparation and indicate that the mitochondria play an important role in the accumulation of basic drugs in the lung.     

Interaction of the Macrolide Antibiotic Azithromycin with Lipid Bilayers: Effect on Membrane Organization,Fluidity, and Permeability

No HeadingPurpose. To investigate the effect of a macrolide antibiotic, azithromycin, on the molecular organization of DPPC:DOPC, DPPE:DOPC, SM:DOPC, and SM:Chol:DOPC lipid vesicles as well as the effect of azithromycin on membrane fluidity and permeability.Methods. The molecular organization of model membranes was characterized by atomic force microscopy (AFM), and the amount of azithromycin bound to lipid membranes was determined by equilibrium dialysis. The membrane fluidity and permeability were analyzed using fluorescence polarization studies and release of calcein-entrapped liposomes, respectively.Results. In situ AFM images revealed that azithromycin leads to the erosion and disappearance of DPPC and DPPE gel domains, whereas no effect was noted on SM and SM:cholesterol domains. Although azithromycin did not alter the permeability of DPPC:DOPC, DPPE:DOPC, SM:DOPC, and SM:Chol:DOPC lipid vesicles, it increased the fluidity at the hydrophilic/hydrophobic interface in DPPC:DOPC and DPPE:DOPC models. This effect may be responsible for the ability of azithromycin to erode the DPPC and DPPE gel domains, as observed by AFM.Conclusions. This study shows the interest of both AFM and biophysical methods to characterize the drug-membrane interactions.     

PDCA循环原理下医院基本药物制度推行对合理用药的影响

目的 探讨PDCA循环管理方法在医院基本药物管理中的应用及其对合理用药的影响。方法 通过制定和推行一系列国家基本药物制度的落实方案及措施,运用PDCA循环原理策略加强各项干预计划的落实,考察实施后医院基本药物使用情况及合理用药的变化情况。结果 经过PDCA循环管理后,医院基本药物品种遴选比例、基本药物临床配备率、基本药物使用率、基本药物使用金额比分别由2013年的54.5%,32.4%,23.0%,17.6%上升为2015年上半年的75.07%,45.25%,45.57%,29.29%;医院药占比由2013年的40.12%下降至36.67%,临床用药合理性不断提高。结论 PDCA循环有效促进了医院基本药物优先、合理使用。     

利用时辰药理指导合理用药

目的：论述人体生物节律与时辰药理学的关系，为，临床选择最佳用药时间提供参考。方法：参考有关文献和资料，结合临床用药，进行分析总结。结果：依据人体的生物节律性，药物具有最佳的服药时间。结论：临床用药应按照人体的生物节律和药物的作用时辰选择最佳的给药时间、给药方案，不仅可以提高疗效，减少药物的用量，还可以减少药物不良反应的发生。     

Characterization of Interactions Between Bile Salts and Drugs by Micellar Electrokinetic Capillary Chromatography. Part I.

Purpose. The general properties of micellar electrokinetic capillary chromatography (MECC) were utilized to characterize the strength of interactions between bile salts and biological active substances. Methods. For that purpose various bile salts were used as micellar pseudostationary phase in the background electrolyte. Furthermore, a physicochemical model was applied and the effective partition coefficients between micellar and water phase were calculated in order to evaluate the strength of interactions between bile acids and the drugs. Results. It was found that the interactions between the selected drugs and bile salts depend both on the lipohilicity of the drugs and on the charge of the components. Only hydrophobic, cationic drugs such as quinine and propranolol are able to interact with these surface-active agents. Conclusions. MECC is a valuable methode to characterize interactions such occurring between drugs and bile salts.     

基层特殊管理药品监管现状回顾及存在问题的分析

特殊管理药品涵盖麻醉药品、精神药品、医疗用毒性药品及放射性药品、药品类易制毒化学品等范畴,存在涉及面广、涵盖品种多、风险性大等特点。基层监管部门肩负辖区药品使用、经营、科研单位监管职责。其监管重点、侧重不尽相同。本文通过汇总辖区特殊管理药品的数据,对监管现状进行回顾性分析。     

壳聚糖和壳聚糖-EDTA轭合物双层包覆脂质体对胰岛素口服吸收的影响

目的研究壳聚糖和CEC双层包覆胰岛素脂质体的吸收状况,并验证其有效性。方法采用逆相蒸发制备胰岛素脂质体;用酶-苯酚法测定血糖值;用放射免疫法测定血清胰岛素含量,并采用Pkanalyst程序进行拟合。结果 Ch-CEC双层包覆的胰岛素脂质体对负载葡萄糖的正常大鼠的血糖升高具有抑制作用;以皮下注射胰岛素(Ins)为对照,Ch-CEC双层包覆的胰岛素脂质体经糖尿病模型大鼠和beagle犬给药后的相对药理生物利用度均大于9%,具有较好的降血糖作用。另外,在beagle犬降血糖实验中,根据血清胰岛素浓度-时间曲线的曲线下面积(AUC)计算Ch-CEC双层包覆的胰岛素脂质体灌胃给药的相对生物利度为12.67%。结论壳聚糖-CEC双层包覆胰岛素脂质体有利于改善胰岛素口服生物利用度。