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。     

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。     

我院2011-2013年质子泵抑制剂应用分析

目的:为临床合理使用质子泵抑制剂(PPIs)和医药产业政策调整提供参考。方法:采用回顾性方法,对我院2011-2013年PPIs的销售金额、用药频度(DDDs)和日均费用(DDC)等进行统计分析。结果:PPIs的销售金额和DDDs呈快速增长态势,年均复合增长率为46.47%。口服PPIs的销售金额和DDDs占比分别为31.22%、84.25%,注射用PPIs的销售金额和DDDs占比分别为68.78%、15.75%。3年销售金额排前3位的是注射用泮托拉唑、奥美拉唑和兰索拉唑(29.81%、21.36%、13.81%);3年DDDs排前3位的是奥美拉唑、兰索拉唑和雷贝拉唑口服剂(35.00%、28.84%、14.03%)。结论:奥美拉唑和兰索拉唑用量相对较大,但不可忽视临床存在注射剂过度使用、无指征用药、使用疗程过长和用法用量不合理现象。     

近年来质子泵抑制剂的研究进展

概述了质子泵抑制剂（PPIs)作为临床应用最广泛的抗酸药物的作用机制,以及各种不同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临床应用特点。     

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。     

2020～2022年漳州市某医院质子泵抑制剂用药分析

目的 分析2020～2022年漳州市某医院质子泵抑制剂(PPIs)的使用情况及发展趋势,为临床合理用药提供参考。方法 对2020～2022年我院PPIs的用药金额、用药频度(DDDs)、日均费用(DDC)和药品排序比(B/A)进行统计分析。结果 PPIs用药金额总体呈逐年递减趋势;泮托拉唑钠肠溶片、奥美拉唑肠溶胶囊和雷贝拉唑钠肠溶片的DDDs居前3位;连续3年艾普拉唑肠溶片的DDC最高,B/A最低,奥美拉唑肠溶胶囊DDC最低,B/A均大于1。结论 PPIs在我院的应用基本合理,但仍需要兼顾疗效和成本,进一步规范和完善PPIs的临床管理与应用。     

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。     

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。     

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     

质子泵抑制剂的临床应用相关研究进展

<正> 自1988年奥美拉唑(Omeprazole)上市以来,质子泵抑制剂(Proton pump inhibitors,PPIs)的研发工作不断取得进展,先后又有兰索拉唑(Lanso-prazole)、泮托拉唑(Pantoprazole)、雷贝拉唑(Rabeprazole)、埃索美拉唑(Esomeprazole)、来米诺拉唑(Leminorazole)等新药上市,该类药物对基础、夜间胃酸和五肽胃泌素、试餐等刺激的胃酸分泌有极明显的抑制作用,是目前已发现的作用最强的一类胃酸分泌抑制剂。PPIs的研发成功,成为20世纪胃肠病学研究的重要进展之一。可以说PPIs是临床治疗酸相关性疾病的有力武器。本文就该类药     

Proton pump inhibitor-induced acute interstitial nephritis

What is already known about this subject

• In several case reports the use of omeprazole has been associated with interstitial nephritis.
• Recently there have been reports linking other proton pump inhibitors (PPIs) with interstitial nephritis.

What this study adds

• We present supplementary cases received by the Netherlands Pharmacovigilance Centre Lareb, concerning interstitial nephritis in users of PPIs including omeprazole, pantoprazole and rabeprazole.
• In this case series seven patients are presented. In six cases they recovered spontaneously after cessation of the PPI, in one case the patient recovered after treatment with a corticosteroid.
• Further support for this association comes from the worldwide adverse drug reaction database of the World Health Organization.
• This report shows that interstitial nephritis can occur with all PPIs. Health professionals should be aware of this potential serious adverse drug reaction.

Aim

To investigate the association between the use of proton pump inhibitors (PPIs) and acute interstitial nephritis (AIN).

Methods

The Netherlands Pharmacovigilance Centre Lareb received seven case reports of AIN induced by various PPIs. In five of the reports it was mentioned that the diagnosis was confirmed by a renal biopsy.

Results

The time to onset varied between hours to 4 months. In all cases but one the patient spontaneously recovered after withdrawal of the offending agent. In one case the patient received treatment with prednisolone and recovered. In one patient a rechallenge was done 9 days after the initial event. Within 12 h of re-exposure the patient developed symptoms of AIN.

Conclusions

The mechanism of drug-induced AIN is unknown, but an immunological mechanism is suspected. Our reports show no relation between dosage, latency, time to recovery, age or gender, supporting the hypothesis that the aetiology of AIN is immunological. Lareb has received reports of AIN with the use of omeprazole, pantoprazole and rabeprazole. This shows that AIN is a complication associated with the whole group of PPIs and not only omeprazole. It is important for health professionals to be aware of this adverse drug reaction, because an accurate and timely diagnosis and withdrawal of the offending drug can prevent potentially life-threatening renal failure.     

质子泵抑制剂治疗婴儿胃食管反流性疾病安全性的Meta分析

目的：探讨质子泵抑制剂（PPIs）在治疗婴儿胃食管反流性疾病（GERD）中的安全性。方法：收集已发表的有关使用PPIs治疗婴儿GERD发生药物不良反应（ADR）的研究,对检索到的原始资料进行质量评估,对总ADR以及单个ADR进行分析。结果：共纳入4篇文献,总样本量为617例,其中PPIs组352例,安慰剂组265例。总ADR的RR值为1.27,可信区间为（1.06,1.51）,P=0.008,单个ADR中除发热外,其余PPIs组与安慰剂组无显著性差异。结论：质子泵抑制剂在治疗婴儿GERD过程中总ADR发生概率高于安慰剂组,但因纳入研究较少、质量尚缺乏、样本含量小,需要更多高质量的随机对照试验以及观察性研究去进一步论证。     

急性心肌梗死患者应用质子泵抑制剂的利用评价及用药分析

目的：分析急性心肌梗死患者质子泵抑制剂（PPI）的使用情况,建立药物利用评价标准。方法：收集我院心血管内科2013年1月~2014年6月出院的急性心肌梗死患者的病例资料,对PPI的使用情况进行分析。结果：共纳入291例患者,PPI使用率91.4%,平均用药（10.3±4.2） d,给药方式口服、静脉继以口服为主,静脉途径多用泮托拉唑,平均剂量（54.0±19.2） mg·d^-1,口服途径多用雷贝拉唑,平均剂量（18.1±4.2） mg·d^-1。结论：我院心梗患者PPI使用率高、疗程较长,选药品种及用法用量基本合理;需加强对给药剂量和疗程的控制。     

免疫检查点抑制剂致急性肾损伤的研究进展

免疫检查点抑制剂(ICPi)是一种靶向作用于表达在T细胞表面的免疫抑制分子的单克隆抗体,其作为一种新兴的免疫治疗药物,已广泛用于治疗各种实体肿瘤和血液系统肿瘤.然而,ICPi也导致了一类新的自体免疫相关不良反应的发生,一般称之为免疫治疗相关不良反应(irAEs).急性肾损伤(AKI)为ICPi常见的irAEs之一,本文...     

某院急诊注射用质子泵抑制剂的临床应用分析

目的：对某院急诊注射用质子泵抑制剂（PPIs）的使用情况进行分析,为临床合理用药提供参考。方法：采用回顾性调查研究的方法,检索某院HIS,获取2015年7月份使用过注射用PPIs的急诊患者处方,依据SAHP（美国医院药师协会）指南及药品说明书对其临床应用进行合理性分析。结果：在1 754份处方中,统计结果显示某院急诊使用PPIs注射剂的临床诊断不符合使用指征占比24.7%,用法用量不合理的处方占比7.5%,联合用药不合理占比为1.7%,老年患者使用潘妥洛克日剂量超40 mg一项为5.4%,具有统计学意义,其合理性有待进一步讨论研究。结论：某院急诊科使用注射用质子泵抑制剂存在不合理现象。为减轻患者经济负担及降低用药风险,临床医生应规范诊疗行为,做到诊断与用药相适应,杜绝无正当理由超适应证用药;可通过处方点评或信息系统引导用药等干预措施来改善目前的用药现状。     

Impact of Acid-Reducing Agents on Gastrointestinal Physiology and Design of Biorelevant Dissolution Tests to Reflect These Changes

BackgroundOf the various drug therapies that influence gastrointestinal (GI) physiology, one of the most important are the acid-reducing agents (ARAs). Because changes in GI physiology often influence the pharmacokinetics of drugs given orally, there is a need to identify in vitro methods with which such effects can be elucidated.ObjectiveLiterature concerning the effects of ARAs (antacids, H₂-receptor antagonists, and proton pump inhibitors [PPIs]) on GI physiology are reviewed with the aim of identifying conditions under which drugs are released after oral administration in the fasted state. In vitro dissolution tests to mimic the effects in the stomach were designed for H₂-receptor antagonists and PPIs.ConclusionsThe impact of ARAs on GI physiology depends on the type, duration, and amount of ARA administered as well as the location in the GI tract, with greatest impact on gastric physiology. While ARAs have a high impact on the gastric fluid pH and composition, changes in volume, viscosity, surface tension, and gastric emptying appear to be less profound. The proposed dissolution tests enable a ready comparison between dosage form performance in healthy adults and those receiving PPIs or H₂-receptor antagonists.     

Gynaecomastia associated with proton pump inhibitors: a case series from the Spanish Pharmacovigilance System.

OBJECTIVE: Proton pump inhibitors (PPIs) are widely used in the management of peptic ulcer and related symptoms. They have been linked to certain endocrine adverse reactions, including gynaecomastia. The aim of the present study is to investigate the association between the use of PPIs and the development of gynaecomastia. METHODS: Reports of cases of gynaecomastia that had putatively been induced by PPIs and that had been collected by the Spanish Pharmacovigilance System via the 'yellow card' scheme, were analysed. Reporting odds ratios (RORs) were calculated as a measure of disproportionality. RESULTS: Twenty-four cases of gynaecomastia associated with PPIs were identified in the database of the Spanish Pharmacovigilance System. Overall, there was a clear temporal sequence of events in all cases and the adverse effect disappeared after drug withdrawal in most of the cases; 14 patients were also receiving other drugs at the time of the adverse effect. The ROR for omeprazole exposure versus no exposure, but not that for other PPIs, showed a statistically significant elevation (ROR adjusted for age 5.23; 95% CI 3.32, 8.26). CONCLUSION: Considering the widespread use of PPIs, gynaecomastia may affect a large number of patients. In most cases, the condition seems to be reversible with drug withdrawal. Doctors should be aware of this potential adverse reaction when prescribing PPIs to their patients over long periods of time.     

质子泵抑制剂致药品不良反应分析

目的:探讨质子泵抑制剂(PPIs)致药品不良反应(ADR)的特点及规律,为临床合理用药提供参考。方法:通过检索1998年1月—2011年6月中国医院数字图书馆(CNKI)收载的主要医药期刊报道的PPIs致ADR案例,得到符合标准的病例113例,并对其进行统计、分析。结果:PPIs所致ADR在41～50岁年龄组较多;用药后4～7d出现的ADR为31例;奥美拉唑致ADR例数最多,占76.99%;ADR可累及机体多个系统,以过敏反应最多(32例,占28.32%),严重者为过敏性休克;ADR预后总体较好。结论:临床应重视PPIs所致ADR,正确认识并全方位监测,可有效减少甚至避免ADR的发生。     

Protective effects of proton pump inhibitors against indomethacin-induced lesions in the rat small intestine

Proton pump inhibitors (PPIs) have been shown to be effective in preventing gastric and duodenal ulcers in high-risk patients taking nonsteroidal anti-inflammatory drugs (NSAIDs); by contrast, scarce information is available concerning the effects of PPIs on intestinal damage induced by NSAIDs in humans or in experimental animals. We examined the effects of lansoprazole and omeprazole on the intestinal injury induced by indomethacin in the conscious rat. PPIs were administered by the intragastric route at 30, 60 and 90 μmol/kg, 12 h and 30 min before and 6 h after indomethacin treatment. The effects of omeprazole and lansoprazole were evaluated on: (1) macroscopic and histologic damage; (2) mucosal polymorphonuclear cell infiltration; (3) oxidative tissue damage and (4) bacterial translocation from lumen into the intestinal mucosa. Lansoprazole and omeprazole (at 90 μmol/kg) significantly decreased (P<0.01) the macroscopic and histologic damage induced by indomethacin in the rat small intestine. Furthermore, both drugs greatly reduced (P<0.01) the associated increases in myeloperoxidase levels and lipid peroxidation induced by indomethacin, whereas they only moderately affected (P<0.05) the translocation of enterobacteria from lumen into the intestinal mucosa. These data demonstrate that omeprazole and lansoprazole can protect the small intestine from the damage induced by indomethacin in the conscious rat. The intestinal protection, possibly related to antioxidant and anti-inflammatory properties of these drugs, may suggest new therapeutic uses of PPIs in intestinal inflammatory diseases.     

质子泵抑制剂致肾脏不良反应研究进展

随着质子泵抑制剂在临床的广泛应用,近年来质子泵抑制剂致急性间质性肾炎和慢性肾脏病的不良反应报道也越来越多,引起了专家的广泛关注。本文主要对质子泵抑制剂致肾脏不良反应的研究进展进行综述。从案例报道和病例回顾角度总结了近年来质子泵抑制剂致肾脏不良反应的临床特点、发病率、发病机制及治疗等,为临床安全用药提供依据。