质子泵抑制剂代谢中细胞色素P-450的作用

质子泵抑制剂（PPI）特异性地作用于H＋·K＋－ATP酶，在胃酸分泌最终步骤中抑制质子泵的功能。PPI被公认为是治疗酸相关性疾病（如消化性溃疡、胃食管反流性疾病（GERD）．Zolling—Eillson综合征等）的最有效药物。对照试验证实：与H２受体拮抗剂相比，PP１可以更好地抑制胃酸分泌、止痛和促进消化性溃疡愈合。PPI在肝脏被充分地生物转化，它们在肝脏中不同程度地被各种细胞色素P－４５０（CYP）同功酶代谢。根据基因多态性表达产物又可将这些酶进一步分为不同亚型。参与PPI代谢的主要同功酶为CYP２C１９和CYP３A４。CYP…     

质子泵抑制剂的分类及药理学特性

选择性抑制胃壁细胞上H^＋/-ATP酶的药物-质子泵抑制剂已成为一代新型抑酸药物,是目前治疗酸相关疾病（消化性溃疡、反流性食管炎等）以及非甾体类抗炎药相关胃肠病变的首选药物。自1988年第一个质子泵抑制剂奥美拉唑上市以来,全球共相继上市了兰索拉唑、泮托拉唑、雷贝拉唑、埃索美拉唑等8个品种,而现在国内上市的质子泵抑制剂有5个。尽管各个质子泵抑制剂拥有共同的苯并咪唑内核及吡啶环的化学结构,但它们在药代动力学和药效学上仍有细微差异。本文就国内已上市的质子泵抑制剂的药理学特性作一简要概述,以期促进质子泵抑制剂在临床上的合理选用。     

临床常用质子泵抑制剂的研究进展

目的介绍临床常用质子泵抑制剂的药理和临床应用研究进展。方法通过查阅文献的方法,对临床常用质子泵抑制剂奥美拉唑、泮托拉唑、兰索拉唑、雷贝拉唑和埃索美拉唑的在药代动力学、药理作用和临床应用等方面进行比较。结果临床常用的这5种质子泵抑制剂在药代动力学、药理作用和临床应用等方面存在差异。结论临床在应用这5种质子泵抑制剂时,应依据药物各自的特点合理选用药物。     

质子泵抑制剂的安全性与合理应用

本文根据近年文献报告,对5种质子泵抑制剂的作用特点、药代动力学、不良反应及相互作用进行综合比较,为临床安全合理用药提供依据。     

新型质子泵抑制剂——埃索美拉唑

质子泵抑制剂穴PPI雪是20世纪80～90年代治疗酸相关性疾病的一个重要进展,对溃疡病、胃食管反流病穴GERD雪和胃泌素瘤等的内科治疗是一个突破。埃索美拉唑,商品名耐信。它是奥美拉唑的S型光学异构体,由于其药代动力学的特点,治疗GERD优于目前已有的4种PPI眼1演。1.药代动力学奥美拉唑是R型和S型两种光学异构体1押1的混合物,而埃索美拉唑是单一的S型异构体,其特点为口服后的首过效应少,生物利用度和血浓度较奥美拉唑或R型异构体为高,因此,药效较奥美拉唑高而持久。本品在小肠内吸收,单次口服本品的血药浓度达峰时间穴Tmax雪为1～2h,…     

质子泵抑制剂的合理应用及其影响因素

目的探讨质子泵抑制剂(PPI)作用的影响因素,促进临床合理用药。方法综述PPI的作用原理及临床应用研究,探讨质子泵抑制剂的药效影响因素。结果 PPI的药效与用药时间、患者的情绪及基因多态性等多种因素有关。结论临床合理用药方案的制定应综合考虑多方面因素。     

质子泵抑制剂对乙型肝炎后肝硬化患者预后的影响分析

目的探究对乙型肝炎后肝硬化患者使用PPI后对患者肝脏功能以及临床症状的影响。方法选取2012年1月至2015年1月来我院就诊的乙型肝炎后肝硬化患者120例为研究对象,对其使用PPI治疗前后的临床症状,不良反应,并发症以及凝血功能等情况进行全面分析,探究患者在使用PPI之后临床症状的改善情况。结果腹水人数从之前的40例下降为3例,乏力人数从之前的49例下降为4例,纳差从之前的31例下降为6例,其患者率分别为92.5%,91.84%和80.65%和治疗前相比,患者Child-pugh评分与治疗前相比得到明显改善,其中A级从之前的45例下降为10例,B级从之前的44例转变为72例,C级从之前的31例转变为38例。和治疗前相比,患者TBIL呈现下降趋势,而ALB呈现出上升趋势。但组间数据无统计学意义存在。患者纤维连接蛋白,胆碱酯酶,以及凝血酶原时间等相关治疗在接受PPI治疗前后无明显统计学意义存在(P>0.05)。出现自发性腹水者13例,肝肾综合征者人数为8例,出现肝脑病患者人数为15例。结论使用PPI对患者进行治疗,能够在一定程度上减少肝损害现象,促进肝细胞再生,利用该药物不会增加患者本身并发症的发生率,预后效果良好,值得推广。     

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     

苯并咪唑质子泵抑制剂的临床应用

质子泵抑制剂（ＰＰＩ）因其作用机制独特,作用特异性高,抑酸作用强,持续时间久而被广泛用于与酸有关的各种紊乱性疾病。其对消化性溃疡的疗效超过了Ｈ２受体拮抗剂,使消化性溃疡的治疗发生了重大变革。目前研制开发中的ＰＰＩ主要有两大类：ＡＴＰ拮抗型和Ｋ＋拮...     

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。     

General pharmacology of IY-81149, a new proton pump inhibitor

IY-81149 (2-[(4-methoxy-3-methyl)-2-pyridinyl]methylsulfinyl -5-(1H-pyrrol-1-yl)-1H-benzimidazole, CAS 172152-36-2) is a new proton pump inhibitor and expected to be an antiulcer drug. Its general pharmacological effects were studied in this paper. The doses given were vehicle control, 0.3, 1, 3, 100, 300 and 1000 mg/kg and were administered orally. The animals used in this study were mouse, rat, guinea pig and beagle dog. IY-81149 decreased spontaneous locomotor activity at 1000 mg/kg and showed a weak effect in motor performance at 300 and 1000 mg/kg. IY-81149 prolonged the hexobarbital-induced sleeping time dose dependently at 100, 300 and 1000 mg/kg. Oral administration of IY-81149 caused a dose-dependent hypothermic effect up to 300 mg/kg and showed analgesic effect at 1000 mg/kg. IY-81149 produced an antisecretory effect in pylorus ligated rats. The total gastric volume and acidity were significantly decreased at doses ranging from 1 to 3 mg/kg. However, IY-81149 had no effects on general behavior, did not show anticonvulsant activity, and did not affect blood pressure and heart rate, LVP (left ventricular peak systolic pressure), LVEDP (left ventricular end diastolic pressure), LVDP (left ventricular developing pressure), DP (double product), HR (heart rate), CFR (coronary flow rate), smooth muscle contraction, respiration, intestinal transport and renal function. These findings demonstrate that IY-81149 possesses weak central nervous system action and inhibitory effects on microsomal enzymes and gastric secretion after single administration. The results suggest that IY-81149 does not exert any notable pharmacological effects on the cardiovascular system, autonomic nerve system or smooth muscle function at all doses tested.     

Effect of a proton pump inhibitor on the pharmacokinetics of imatinib

AIMS

Imatinib mesylate (Gleevec®/Glivec®), which has revolutionized the treatment of chronic myeloid leukemias (CML) and gastrointestinal stromal tumours (GIST), has been reported to cause gastric upset. Consequently, proton pump inhibitors (PPI) are frequently co-administered with imatinib. Because PPI can elevate gastric pH and delay gastric emptying or antagonize ATP-binding-cassette transporters, they could influence imatinib absorption and pharmacokinetics. We aimed to evaluate whether use of omeprazole has a significant effect on imatinib pharmacokinetics.

METHODS

Twelve healthy subjects were enrolled in a two-period, open-label, single-institution, randomized cross-over, fixed-schedule study. In one period, each subject received 400 mg imatinib orally. In the other period, 40 mg omeprazole (Prilosec®) was administered orally for 5 days, and on day 5 it was administered 15 min before 400 mg imatinib. Plasma concentrations of imatinib and its active N-desmethyl metabolite {"type":"entrez-protein","attrs":{"text":"CGP74588","term_id":"875877231"}}CGP74588 were assayed by LC-MS, and data were analyzed non-compartmentally.

RESULTS

PPI administration did not significantly affect the imatinib area under the plasma concentration vs time curve (AUC) (34.1 µg ml⁻¹ h alone vs 33.1 µg ml⁻¹ h with omeprazole, P= 0.64; 80% power), maximum plasma concentration (C_max) (2.04 µg ml⁻¹ alone vs 2.02 µg ml⁻¹ with omeprazole, P= 0.97), or half-life (13.4 h alone vs 14.1 h with omeprazole, P= 0.13).

CONCLUSIONS

Our results indicate that the use of omeprazole does not significantly affect the pharmacokinetics of imatinib, as opposed to, for example, dasatinib where PPI decreased AUC and C_max two-fold.     

质子泵抑制剂长期应用的安全性研究进展

质子泵抑制剂是治疗酸相关性疾病的首选药物,由于其显著的疗效和良好的安全性,临床应用越来越广泛,处方量与日俱增。但近几年来,质子泵抑制剂长期应用导致的潜在不良反应(如营养素缺乏、骨质疏松症、呼吸道和肠道感染、胃底腺息肉等)备受关注,也颇具争议。本文就质子泵抑制剂长期应用的安全性研究进展做一综述。     

质子泵抑制剂点评模式及制度的建立与效果分析

目的探讨质子泵抑制剂专项点评的有效性,建立长效机制以促进质子泵抑制剂的合理使用。方法建立质子泵抑制剂处方点评表格、点评模式、制度,对2014年及2015年7-12月使用了质子泵抑制剂的出院病历进行随机抽样,各抽取200份,共400份病历进行点评,对质子泵使用率、使用强度、合理率、平均分进行对照研究。结果从2014年实施质子泵抑制剂专项点评模式后,质子泵抑制剂使用强度从2014年的67.78下降到60.65,合理率从2014年的31.5%上升到43.0%、处方平均分从51.99提高到74.19。与2014年相比,质子泵抑制剂不合理使用情况均有下降,无适应证、无指征预防用药等一票否决缺陷及重度缺陷下降最为明显。结论质子泵抑制剂处方专项点评模式的建立与实施,促进了质子泵抑制剂的合理使用,可作为质子泵抑制剂的临床应用管理的长效机制。     

Effects of two benzimidazoles as proton pump inhibitors on water immersion stress-induced gastric ulcers in rats.

This study was designed to clarify effects of proton pump inhibitors, E-3810(2-([4-(3-methoxypropoxy)-3methylpyridine-2-yl]methyl- sulfinyl)-1H-benzimidazol sodium salt) and omeprazole (CAS 73590-58-6), on water immersion stress-induced gastric ulcers in relation to mucosal prostaglandins (PGs) and leukotrienes (LTs). Mucosal PGs were measured by high performance liquid chromatography (HPLC). In untreated rats, 4 kinds of PGs, i.e., 6-keto-PGF1 alpha, PGF2 alpha, PGE2 and PGD2 were detected in gastric mucosa, but no LTs were detected. Water immersion stress for 6 h caused severe hemorrhagic lesions in the fundic portion and, concomitantly, significant decreases in mucosal PG levels. On the other hand, LTC4 and LTD4 were detected after 6 h stress treatment, though LTB4 and LTE4 were not detected throughout the experiments. Peptide-LT (the sum of LTC4 and LTD4) levels were 23.5 +/- 3.2 ng/g tissue 6 h after water immersion stress. Administration of 20 mg/kg of E-3810 or 20 mg/kg of omeprazole mitigated gastric lesions and increases in the mucosal peptide-LT levels, but dit not improve the decrease in mucosal PGs.