质子泵抑制药药动学的研究进展

质子泵抑制药(PPIs)是临床中主要的抑酸药,奥美拉唑、埃索美拉唑、兰索拉唑、泮托拉唑、雷贝拉唑等PPIs在药动学方面存在很大的差异(如生物利用度、代谢型、药物的相互作用、生物特异性等方面)。近年来,有很多文献报道了P450酶(CYP)代谢对PPIs的药动学影响。临床证据证明PPIs安全有效,但仍有很多患者对PPIs耐药,所以在实践中应该选择性应用PPIs。     

苯并咪唑类质子泵抑制剂的药理和临床研究进展

从药理作用、药动学、临床应用及安全性等方面综述质子泵抑制剂（PPIs）的研究进展，比较了各种不同PPIs包括奥美拉唑、兰索拉唑、泮托拉唑、雷贝拉唑、莱米诺拉唑和吡帕拉唑等的相应特点。     

某院2016~2018年质子泵抑制剂应用情况调查分析

目的调查医院质子泵抑制剂(PPIs)临床使用情况,分析PPIs临床应用趋势,为临床合理使用提供参考。方法从医院HIS系统中调取2016~2018年PPIs的全部销售记录,并对其销售金额、用药频度(DDDs)、限定日费用(DDC)、年消耗量等指标进行分析。结果2016~2018年PPIs销售无论是金额还是占药品总销售金额比例都呈逐年下降趋势,PPIs销售金额下降率2017年为18.28%,2018年为9.34%。结论PPIs使用基本合理。临床使用仍倾向于第一代PPIs奥美拉唑,泮托拉唑、雷贝拉唑因对CYP2C19抑制性较小也逐步被临床认可。     

质子泵抑制剂与急性间质性肾炎

质子泵抑制剂(proton pump inhibitors,PPIs)致急性间质性肾炎(acute interstitial nephritis,AIN)是一种罕见而严重的药物不良事件.目前临床使用的PPIs如奥美拉唑、埃索美拉唑、泮托拉唑、雷贝拉唑和兰索拉唑都可致AIN,其中以奥美拉唑报道最多.PPIs致AIN的临床...     

2011-2014年我院住院患者质子泵抑制剂应用情况分析

目的:调查和分析我院住院患者质子泵抑制剂(PPIs)的应用情况,评价近年我院PPIs临床应用的趋势并分析其合理性,为临床用药提供参考。方法:利用医院阳光用药监控平台提供的2011-2014年PPIs的品种、年消耗量、销售金额等数据,用限定日剂量(DDD)法,统计用药频度(DDDs)、人均DDDs、日均费用(DDDc)、药物利用指数(DUI)等,进行综合分析。结果:2011-2014年我院各类PPIs总销售金额逐年增加,2012年的增幅最明显。第2代PPIs产品埃索美拉唑、雷贝拉唑的使用呈逐年上升趋势,占主导地位的仍是第1代PPIs,相对于第2代PPIs,特别是口服制剂,有明显的价格优势。住院患者PPIs的应用有向口服制剂为主的发展趋势,仅奥美拉唑仍以注射剂应用为主。各年度PPIs的DUI均大于1.0。结论:我院的PPIs品种在临床选用上符合"有效、经济"的合理用药原则,但从人均DDDs及DUI分析,存在超剂量应用的现象。     

2013-2015年某三甲医院质子泵抑制剂使用情况分析

目的:通过对某三甲综合医院2013-2015年质子泵抑制剂(proton pump inhibitors,PPIs)使用情况分析,为临床合理用药及科学管理提供参考依据。方法: 从医院信息系统调取2013-2015年医院PPIs的品种、规格、剂型、数量、销售金额等数据,进行评价分析。结果: 2013-2015年医院PPIs总销售金额、总用药频度(defined daily dose system,DDDs)呈逐年增长趋势,销售金额及DDDs排序前３位的药品分别是注射用泮托拉唑钠、注射用兰索拉唑、雷贝拉唑钠肠溶胶囊,PPIs注射剂的销售金额及DDDs所占比重较高。埃索美拉唑镁肠溶片销售金额增长迅速。连续3年注射用埃索美拉唑钠限定日费用(defined daily cost,DDC)最高,其它药品的DDC呈平稳趋势,多数PPIs的排序比≥1.0。结论: 2013-2015年医院PPIs临床使用基本合理,但存在临床倾向于使用注射剂和部分品种加重患者经济负担现象,需进一步加强和完善PPIs临床应用与管理。     

2018年某院住院患者口服质子泵抑制剂的临床用药分析

目的:分析我院住院患者使用口服质子泵抑制剂(PPIs)的情况及其合理性。方法:回顾性分析我院口服PPIs的应用情况。结果:2018年我院住院患者口服PPIs的销售金额从高到低排序为济诺(雷贝拉唑肠溶胶囊)、波利特(雷贝拉唑钠肠溶片)、奥克(奥美拉唑肠溶胶囊)、耐信(艾司奥美拉唑镁肠溶片)、洛赛克(奥美拉唑镁肠溶片);用药频度(DDDs)排序从高到低为济诺、奥克、波利特、耐信、洛赛克。结论:2018年我院住院患者使用口服PPIs是合理的,济诺作为第二代PPIs,在我院具有更多临床应用。     

2011年杭州地区12家医院质子泵抑制药用药合理性分析

目的：了解杭州地区12家医院2011年质子泵抑制药（PPIs）用药的现状及合理性。方法：采用金额排序、用药频度（DDDs）排序,了解该地区12家医院PPIs使用情况;制定PPIs合理用药评价标准,评价PPIs用药合理性。结果：该地区12家医院PPIs使用量泮托拉唑〉奥美拉唑〉埃索美拉唑镁〉雷贝拉唑〉兰索拉唑;PPIs处方数31 929张,不合理处方13 535张。不合理使用主要表现为用药指征不合理（60.53%）、用法不合理（17.63%）、用量不合理（9.46%）。结论：该地区PPIs使用存在较多不合理之处,建议颁布PPIs使用规范,同时加强监督管理,确保临床合理用药。     

老年消化性溃疡患者长期应用质子泵抑制剂对骨质疏松的影响

<正>质子泵抑制剂(PPIs)是一类作用于胃H+-K+ATP酶的强效抑酸药,临床常用药物包括奥美拉唑、兰索拉唑、埃索美拉唑、泮托拉唑及雷贝拉唑等~([1])。传统认为,PPIs用于治疗幽门螺旋杆菌相关的消化性溃疡疾病,不良反应轻微,部分患者可以长期服用此类药物对病情进行控制。近期有研究表明,患者长期使用PPIs后,可影响维生素及钙的吸     

某三甲医院抑酸剂的使用情况分析

目的系统分析西安市某三甲医院H2受体阻滞剂(H2RAs)和质子泵抑制剂(PPIs)的使用情况,为临床合理用药提供参考依据。方法从该院信息管理系统(HIS)中提取2017年H2RAs和PPIs的用药数据,计算用药频度(DDDs)和限定日费用(DDC)等药物经济学指标,进行回顾性分析。结果该医院使用抑酸剂99%以上是PPIs,几乎很少使用H2RAs。门诊患者使用口服抑酸剂的比例占93%,住院或急诊患者用静脉抑酸剂的比例占99%。PPIs全年的销售金额达到5 000多万元。其中静脉用药的销售金额为89%左右,使用量排名前3位的是兰索拉唑、泮托拉唑和雷贝拉唑,DDDs排名前3位的是兰索拉唑、泮托拉唑和奥美拉唑,DDC排序前3位的是雷贝拉唑(256.5元)、埃索美拉唑(118.23元)和兰索拉唑(84.8元)。口服PPIs用量排名前3位的是泮托拉唑、兰索拉唑和奥美拉唑,DDC排序前3位的是雷贝拉唑(26.84元)、埃索美拉唑(11.26元)和奥美拉唑(7.15元)。结论该三甲医院抑酸剂主要使用PPIs,静脉使用过多,销量较大的几种静脉用PPIs的DDC值较高,不符合社会性及经济性的需求。兰索拉唑与其他PPIs相比无优势,但销售金额占50%,存在滥用现象。建议进一步加强PPIs的点评机制,促进其安全、有效使用。     

DISTRIBUTION AND ACCUMULATION OF A MIXTURE OF ARSENIC,CADMIUM, CHROMIUM,NICKEL, AND VANADIUM IN MOUSE SMALL INTESTINE,KIDNEYS, PANCREAS,AND FEMUR FOLLOWING ORAL ADMINISTRATION IN WATER OR FEED

Manufactured gas plant (MGP) sites are contaminated with coal tar and may contain metals such as arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), and vanadium (V). These metals are known to cause cancer or other adverse health conditions in humans, and the extent and cost of remediating MGP sites may be influenced by the presence of these metals. Studies assessed the distribution of these metals in female B6C3F1 mice ingesting (1) a metal mixture in water or (2) an MGP mixture in NIH-31 feed. The highest metal levels were measured in the small intestine and kidneys of mice receiving the metal mixture in water. For mice receiving the metal mixture in water, levels of As, Cd, and Cr, in the small intestine, levels of As, Cd, Cr, and V in the kidneys, levels of As and Cd in the pancreas, and levels of Cr and V in the femur were significantly greater than controls at 4, 8, 12, 16, and 24 wk. Except for Ni levels in the small intestine and femur and Cr levels in the kidneys, levels of metals were much lower in mice administered the MGP mixture in feed. The highest concentrations of metals in mice ingesting the MGP mixture in feed were found in the small intestine and kidneys, but few were significantly greater than controls. Levels of As in the small intestine at 6 and 18 wk and levels of Cr in the kidneys at 12, 18, and 24 wk were significantly greater than in controls. The data suggest that tissue burdens in small intestine, kidneys, pancreas, and femur of arsenic, cadmium, chromium, and vanadium are less when metals are present as an MGP mixture in feed than as a mixture in water. The reduced distribution and accumulation of metals in the organs of mice ingesting the MGP mixture in feed compared to the levels in organs of mice ingesting the metal mixture in water suggests that metals may be less likely to accumulate in humans ingesting MGP mixtures, thereby presenting a lower overall human health risk. The data presented indicate that the matrix in which metals are present will affect the uptake of individual metals and the organ specificity.     

Clinical evaluation of imipenem/cilastatin sodium against severe infections complicated with hematological disorders and solid tumors

Imipenem/cilastatin sodium (IMP/CS) was administered to patients with severe infections complicated by hematological disorders and solid tumors to assess its efficacy and safety. Primary diseases in this series of 76 cases included 37 cases of hematological disorders (acute leukemia in 25 cases, malignant lymphoma in 7 cases, aplastic anemia in 3 cases and 2 other diseases) and 38 cases of solid tumors (lung cancer in 7 cases, gastric cancer in 11 cases, esophageal cancer in 6 cases, pancreatic cancer in 3 cases, bile duct cancer in 4 cases, hepatocellular cancer in 3 cases, and 4 other diseases). Following results were obtained. 1. Types of infection in hematological diseases were sepsis in 5 cases, suspected sepsis in 24 cases, pneumonia in 5 cases and 3 others. The efficacy rates were 100% in sepsis, 62.5% in suspected sepsis, 80% in pneumonia and 73% in all cases. 2. Types of infection in solid tumors were sepsis in 2 cases, suspected sepsis in 13 cases, pneumonia in 10 cases, cholecystitis in 2 cases, cholangitis in 5 cases, liver abscess in 2 cases, and 4 others. The efficacy rates were 50% in sepsis, 69.2% in suspected sepsis, 80% in pneumonia, and 71.1% in all cases. 3. IPM/CS was administered in single use in 66 cases and in combination with other antibiotics in 9 cases. The efficacy rate in the single use was 72.7% and that in the combination use was 66.7%. 4. The efficacy rate in 35 cases of first use was 71.4% and that in 40 cases of second use was 72.5%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of capravirine as a CYP3A probe substrate: in vitro and in vivo metabolism of capravirine in rats and dogs.

Metabolism of [(14)C]capravirine was studied via both in vitro and in vivo means in rats and dogs. Mass balance was achieved in rats and dogs, with mean total recovery of radioactivity >86% for each species. Capravirine was well absorbed in rats but only moderately so in dogs. The very low levels of recovered unchanged capravirine and the large number of metabolites observed in rats and dogs indicate that capravirine was eliminated predominantly by metabolism in both species. Capravirine underwent extensive metabolism via oxygenation reactions (predominant pathways in both species), depicolylation and carboxylation in rats, and decarbamation in dogs. The major circulating metabolites of capravirine were two depicolylated products in rats and three decarbamated products in dogs. However, none of the five metabolites was observed in humans, indicating significant species differences in terms of identities and relative abundances of circulating capravirine metabolites. Because the majority of in vivo oxygenated metabolites of capravirine were observed in liver microsomal incubations, the in vitro models provided good insight into the in vivo oxygenation pathways. In conclusion, the diversity (i.e., hydroxylation, sulfoxidation, sulfone formation, and N-oxidation), multiplicity (i.e., mono-, di-, tri-, and tetraoxygenations), and high enzymatic specificity (>90% contribution by CYP3A4 in humans, CYP3A1/2 in rats, and CYP3A12 in dogs) of the capravirine oxygenation reactions observed in humans, rats, and dogs in vivo and in vitro suggest that capravirine can be a useful CYP3A substrate for probing catalytic mechanisms and kinetics of CYP3A enzymes in humans and animal species.     

Pharmacokinetics of a novel butylated hydroxytoluene-thiazolidinone CNS antiischemic agent LY256548 in rats, mice, dogs, and monkeys

Mice, rats, dogs, and monkeys were given a single 50 mg/kg oral dose of [14C]LY256548. Plasma levels of radioactivity and LY256548 were determined, as was the excretion of radioactivity. Peak plasma levels of LY256548 occurred prior to those of radioactivity in mice, dogs, and monkeys, but were coincident in rats. The Cmax of LY256548 in rats, mice, dogs, and monkeys was 0.17, 0.30, 0.04, and 0.02 microgram/ml, respectively. However, the Cmax of radioactivity was 10-fold greater than that of LY256548 in rats and mice, 24-fold greater in dogs, and 40-fold greater in monkeys. The half-lives of LY256548 were substantially less than those of radioactivity in all four species. The oral absorption of LY256548 in rats, dogs, and monkeys was 45%, 7%, and 12%, respectively. The systemic bioavailability of LY256548 in rats, dogs, and monkeys was 6%, 0.4%, and 3%, respectively. Extensive biotransformation of LY256548 was observed in all four species. Fecal excretion of radioactivity was the primary mode of elimination, being 95% in rats, 81% in mice, 100% in dogs, and 68% in monkeys.     

The distribution patterns of trace elements in the blood and organs in a rabbit experimental model of copper pollution and study of haematology and biochemistry parameters

In a rabbit model of five copper overfeeding, we investigated the distribution pattern of trace elements of copper [Cu], zinc [Zn], chromium [Cr], manganese [Mn], and selenium [Se] in blood serum, red cell, and whole blood and in the organs: brain, gallbladder, liver, intestines, heart, kidney, lung, and spleen. Furthermore, their haematology and biochemistry parameters as well as feed consumption and weight development were also performed in this study. Changes in trace element concentrations were determined by contrast and control group. Observably, the increased concentrations of Cr were observed in the heart; that of Cu, Zn, Cr, Mn in the liver; that of Cu, Cr, Mn in the intestines; that of Cu in the spleen; that of Cu in the blood serum; and that of Cu in the whole blood. But remarkably, the decreased concentrations of Mn were observed in heart; that of Zn and Se in the encephalon; that of Cr, Mn and Se in the spleen and that of Zn in the blood serum. In the gallbladder, the concentrations of Zn, Cr, Mn, and Se were also reduced. Excessive Cu was accumulated mainly in liver, intestines, and blood serum. In contrast group, only a few changes were detected in excretion of Mn, Zn, and Cr, but increased concentrations of Cu and Se compared with the control group. For the different biochemistry parameters measured, the contrast group showed changes, mainly owing to the altered activity of enzymes induced by trace element excess and imbalance. Increased concentrations of LDL were measured in contrast group, while a substantial decrease was seen in TG and VLDL as a result of excessive Cu. Regarding haematological parameters, increased concentrations of NEUT% and EO% were found in contrast group, but considerably decreased concentrations were detected in PLT, MONO%, BASO%, MONO#, BASO#, and P-LCR, but a minor decrease was also seen in EO#. The present paper shows the effect of copper pollution in the animals and analyzes the interplay among trace elements in their bodies at length. It is significant for environment protection and toxicology study.     

Distribution of 14C-pethidine in the blood of certain species

Binding of 14C-pethidine to erythrocytes of some species, particularly human, rat and rabbit, was examined in two different concentrations. This binding was investigated by direct measurement of the relative representation in erythrocytes, plasma proteins and the free fraction in blood. In the case of human erythrocytes the relative representation was 33%, in the rat ones 44%, and in the rabbit ones 54%. The fraction bound to plasma proteins was 45% in man, 29% in rats, and 27% in rabbits. The portion of the free fraction was 22% in man, 27% in rats, and 19% in rabbits. The ratio of the concentrations of the fraction bound to erythrocytes and the fraction free in the blood was 1.72 in man, 2.09 in rats, and 3.92 in rabbits. On the basis of these results it can be concluded that binding of pethidine to erythrocytes does not play an insignificant part in total pharmacokinetics of pethidine.     

Valproate-dependent changes in the spectrum of free amino acids in rats: l-carnitine effects

The effect of L-camitine (LC) in a dose of 100 mg/kg on the spectrum of free amino acids in the tissues and blood plasma was studied in rats pretreated for 8 days with valproic acid (VA) in a dose of 200 mg/kg. The VA treatment led to a decrease in the concentration of Ser, Gln, and Ala in the blood plasma and of Gln, Cys, Phe, and His in the liver, and to an increase in the level of Tau, Thr, Gly, alpha-Aba, Ile, and Tyr in the liver. In the rat brain, the concentration of PEA, urea, Ile, Val, Tyr, Phe, and alpha-Aba increased, while the Orn level decreased. The introduction of LC led to correction of the dysbalance of free amino acids, whereby the levels of Asp, Ctn, and Orn in the blood plasma and the levels of Cys and Tyr in the liver were increased, while the levels of Thr, Cly, alpha-Aba, and Ile in the liver and the levels of alpha-Aba, Val, and Phe in the brain were decreased. The character of variation of the spectrum of free amino acids and their derivatives in the tissues and blood plasma of rats confirms the toxicity of VA and shows the ability of LC to normalize (to a certain extent) the balance violated by the VA-induced LC insufficiency.     

Alterations in protein metabolism and amino acid concentrations in rats fed by a high-protein (casein-enriched) diet – Effect of starvation

Rats were fed with a standard laboratory diet (SLD) or a high-protein diet (HPD). After three months changes in amino acid concentration and protein metabolism were examined in fed and 24 h-fasted animals. In the blood of the HPD animals sacrificed in fed state were found higher concentrations of urea, aspartate, taurine, proline, valine, isoleucine, and leucine, and lower concentrations of glycine and cysteine. The main alterations in tissues were decreased concentrations of glycine and increased concentrations of valine, isoleucine, and leucine. Differences in weight, protein concentration, protein synthesis, and proteolysis in tissues were insignificant. The exception was soleus muscle in which higher values of protein synthesis and proteolysis were found in HPD animals. The response to starvation of HPD and SLD fed animals was different. In animals fed before starvation by HPD was found more pronounced decrease in a number of individual amino acids in plasma and tissues and more pronounced decrease in protein synthesis in muscle, spleen, jejunum, and colon. It is concluded that chronic intake of HPD has not positive effect on protein balance in any tissue, results in the imbalance in aminoacidemia in extracellular and intracellular fluid, and alters the response of the organism to starvation.     

Preparation of Alendronate Liposomes for Enhanced Stability and Bioactivity: In Vitro and In Vivo Characterization

Liposomes containing bisphosphonates have been shown to deplete circulating monocytes and reduce experimental restenosis. However, acceptable shelf life was not achieved, and the disruption extent and rate of the vesicles in the circulation has not been examined. Designing an optimal liposomal formulation in general, and for an anti-inflammatory effect in particular, requires careful consideration of the factors that contribute to their in vitro stability and integrity in the blood after injection. An improved liposomal alendronate formulation was prepared by a modified thin lipid film hydration technique followed by extrusion, resulting in relatively smaller size vesicles, narrow size distribution, and low drug to lipid ratio in comparison to the reverse phase evaporation method. In order to rule out premature leakage of the drug, the integrity of the vesicles was examined by means of size-exclusion chromatography in vitro and in vivo, with subsequent analysis of size, drug (fractions of encapsulated and free) and lipid concentrations. Vesicles were found to be stable in serum, with 15 +/- 3% leakage of the drug after 10 min in rabbit's circulation, and intact liposomes were detected in the circulation 24 h following administration. It is concluded that the new formulation results in increased stability (2.5 years) as determined by the insignificant changes in vesicle size, drug leakage, lipid and drug stability, in vitro bioactivity (macrophages inhibition), as well as in vivo in depleting circulating monocytes and inhibition of restenosis in rabbits. Our in vitro stability results regarding dilution in serum paralleled in vivo data. Thus, in vitro assessment may provide a valuable tool in assessing in vivo integrity of liposomal formulations.     

牛樟叶水提物对D-半乳糖致衰老模型小鼠的作用机制研究

目的探讨牛樟叶水提物(AECL)对D-半乳糖致衰老模型小鼠的作用机制。方法取KM小鼠,于颈背部皮下注射D-半乳糖(100 mg/kg,连续20 d),建立衰老小鼠模型。另取10只同批健康小鼠作为正常对照组(A组);模型小鼠随机分为模型组(B组),阳性对照组(C组,维生素E 200 mg/kg),AECL高、中、低剂量组(D1组、D2组、D3组,生药20,10,5 g/kg),各10只。C组、D1组、D2组、D3组小鼠灌胃给药,每日2次,连续30 d;A组和B组给予等体积生理盐水。末次给药2 h后,剖取肝脏、心脏、肾脏和脑,制备成10%组织匀浆,以酶联免疫吸附(ELISA)法检测上述组织、器官匀浆中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)、一氧化氮(NO)和总抗氧化能力(T-AOC)的水平。结果与A组比较,B组小鼠血清中SOD,GSH-Px,T-AOC水平均显著降低(P<0.05);与B组比较,C组、D1组、D2组小鼠血清中SOD和GSH-Px水平均显著升高(P<0.05),C组、D1组T-AOC水平均显著升高(P<0.05)。与A组比较,B组小鼠肝组织匀浆中SOD和CAT水平均显著降低(P<0.05);与B组比较,C组、D1组、D2组、D3组肝组织匀浆中SOD和CAT水平均显著升高(P<0.05)。与A组比较,B组小鼠肾脏组织匀浆中SOD水平显著降低(P<0.05);与B组比较,C组、D2组SOD水平均显著升高(P<0.05)。与A组比较,B组小鼠心脏组织匀浆中SOD显著降低(P<0.05);与B组比较,C组和D2组SOD均显著升高,D1组CAT水平均显著升高(P<0.05)。与A组比较,B组小鼠脑组织匀浆中SOD,GSH-Px,NO水平均显著降低(P<0.05);与B组比较,C组、D1组NO水平均显著升高(P<0.05)。结论AECL具有延缓衰老的作用,其作用机制可能与改善机体心、脑、肝、肾等器官的抗氧化能力有关。