BACKGROUND & AIMS: :Proton pump inhibitors (PPI) are being considered for antineoplastic therapeutic regimens due to their ability to reverse H(+) homeostasis in tumor microenvironment and induce tumor cell death. In order to explore additional mechanism(s) underlying antitumor action of PPI, the present investigation was undertaken to investigate the effect of a PPI pantoprazole (PPZ) on the activation of tumor-associated macrophages (TAM) to tumoricidal state in a murine model of a transplantable T cell lymphoma of spontaneous origin growing in ascitic form. In vivo administration of PPZ to tumor-bearing mice resulted in an enhanced TAM recruitment in tumor microenvironment with M1 macrophage phenotype and augmented activation of TAM to tumoricidal state along with expression of tumor cytotoxic molecules. The study also demonstrates that TAM activating action of PPZ is of indirect nature mediated via its antitumor activity, reversal of tumor-induced immunosuppression and a consequent shift of cytokine balance in the tumor microenvironment favoring polarization of macrophages to M1 type. The study further shows that adoptive transfer of TAM harvested from PPZ-administered tumor-bearing hosts causes an efficient retardation of tumor growth. Possible mechanisms and significance of these observations with respect to the designing of antitumor therapy using PPI are discussed.

背景与目标： : 质子泵抑制剂 (PPI) 因其逆转肿瘤微环境中H () 稳态并诱导肿瘤细胞死亡的能力而被考虑用于抗肿瘤治疗方案。为了探索PPI抗肿瘤作用的其他机制，进行本研究是为了研究PPI泮托拉唑 (PPZ) 对以腹水形式生长的自发起源的可移植T细胞淋巴瘤的鼠模型中肿瘤相关巨噬细胞 (TAM) 活化为杀瘤状态的影响。向荷瘤小鼠体内施用PPZ导致具有M1巨噬细胞表型的肿瘤微环境中TAM募集增强，TAM激活增强至杀瘤状态以及肿瘤细胞毒性分子的表达。研究还表明，PPZ的TAM激活作用是通过其抗肿瘤活性，逆转肿瘤诱导的免疫抑制以及随之而来的肿瘤微环境中细胞因子平衡的转移而间接介导的，从而有利于巨噬细胞向M1型极化。研究进一步表明，从PPZ施用的荷瘤宿主中收获的TAM的过继转移会导致肿瘤生长的有效延迟。讨论了这些观察结果在使用PPI设计抗肿瘤治疗方面的可能机制和意义。

BACKGROUND & AIMS: BACKGROUND:Mechanical ventilation increases risk for bleeding in the upper part of the gastrointestinal tract. Proton pump inhibitors, although they are more potent and longer acting inhibitors of gastric acid production than are histamine(2) antagonists, also are generally more expensive. Data comparing the 2 types of agents for preventing gastrointestinal bleeding in critically ill patients are limited. OBJECTIVES:To compare the effectiveness of famotidine (a histamine(2) antagonist) and pantoprazole (a proton pump inhibitor) in preventing stress ulcers in critically ill patients receiving mechanical ventilation. METHODS:Data were collected from the Project Impact database. All patients who received mechanical ventilation for more than 48 hours from November 2002 to June 2006 and were treated with either drug were included. Patients receiving other drugs or with known bleeding in the upper part of the gastrointestinal tract, thrombocytopenia, or coagulopathy were excluded. RESULTS:A total of 522 patients who received famotidine and 95 who received pantoprazole were included. Bleeding in the upper part of the gastrointestinal tract was more common in patients receiving pantoprazole than in patients receiving famotidine (0.38% vs 3.2%, P= .03). Although scores on the Acute Physiology and Chronic Health Evaluation II were higher in patients who received pantoprazole (P= .01), other outcome measures did not differ significantly between groups. Bleeding in the upper part of the gastrointestinal tract was more frequent among dialysis patients receiving pantoprazole than among those receiving famotidine. CONCLUSIONS:Famotidine and pantoprazole are similarly effective for preventing bleeding in the upper part of the gastrointestinal tract in patients receiving mechanical ventilation.

背景与目标：

BACKGROUND & AIMS: :BACKGROUND AND OBJECTIVE: An increasing trend in prescribing proton pump inhibitors (PPIs) inevitably increases the risk of unwanted drug-drug interactions (DDIs). The aim of this study was to uncover pharmacokinetic interactions between two PPIs-omeprazole and pantoprazole-and venlafaxine. METHODS:A therapeutic drug monitoring database contained plasma concentrations of venlafaxine and its active metabolite O-desmethylvenlafaxine. We considered three groups: a group of patients who received venlafaxine without confounding medications (non-PPI group, n = 906); a group of patients who were comedicated with omeprazole (n = 40); and a group of patients comedicated with pantoprazole (n = 40). Plasma concentrations of venlafaxine, O-desmethylvenlafaxine and active moiety (venlafaxine + O-desmethylvenlafaxine), as well as dose-adjusted plasma concentrations, were compared using non-parametrical tests. RESULTS:Daily doses of venlafaxine did not differ between groups (p = 0.949). The Mann-Whitney U test showed significantly higher plasma concentrations of active moiety, as well as venlafaxine and O-desmethylvenlafaxine, in both PPI groups [p = 0.023, p = 0.011, p = 0.026, +29% active moiety, +27% venlafaxine, +36% O-desmethylvenlafaxine (pantoprazole); p = 0.003, p = 0.039 and p < 0.001, +36% active moiety, +27% venlafaxine, +55% O-desmethylvenlafaxine (omeprazole)]. Significantly higher concentration-by-dose (C/D) values for venlafaxine and active moiety were detected in the pantoprazole group (p = 0.013, p = 0.006, respectively), while in the omeprazole group, C/D ratios for all three parameters-venlafaxine, O-desmethylvenlafaxine and active moiety-were significantly higher (p = 0.021, p < 0.001 and p < 0.001, respectively). CONCLUSIONS:Significantly higher plasma concentrations for all parameters (venlafaxine, O-desmethylvenlafaxine, active moiety) suggest clinically relevant inhibitory effects of both PPIs, most likely on the cytochrome P450 (CYP) 2C19-mediated metabolism of venlafaxine. The findings might be the result of different degrees of CYP2C19 involvement, therefore the inhibition of CYP2C19 by both PPIs may lead to an increased metabolism via CYP2D6 to O-desmethylvenlafaxine.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:The effects of PPIs on human sperm fertilizing capacity were poorly investigated although these drugs are widely over-used. Two publications retrospectively studied relationships between any PPI intake and sperm parameters from patients consulting at infertility clinics, but the conclusions of these reports were contradictory. Only two reports investigated the effects of lansoprazole and omeprazole on sperm motility and found lansoprazole to be deleterious and omeprazole to be neutral for sperm motility. The inconsistency of the PPI effect in the previous reports emphasizes the need for more basic research on human spermatozoa, taking into account the hypothesis that the different PPI drugs may have different effects on sperm physiology. OBJECTIVES:Do PPIs, which are among the most widely sold drug in the word, impact negatively human sperm capacitation and sperm motility? MATERIALS AND METHODS:The effects of PPIs on human sperm maturation and motility were analyzed by CASA, flow cytometry, and Western blot. RESULTS:We tested the impact of 6 different PPIs on human sperm motility and capacitation. We showed that pantoprazole, but not the other PPIs, decreased sperm progressive motility and capacitation-induced sperm hyperactivation. We therefore investigated further the effects of pantoprazole on sperm capacitation, and we observed that it had a significant deleterious effect on the capacitation-induced hyperpolarization of the membrane potential and capacitation-associated protein phosphorylation. DISCUSSION AND CONCLUSION:Our results indicate that exposure to pantoprazole has an adverse effect on the physiological competence of human spermatozoa. As the capacitation process takes place within the female tract, our results suggest that PPIs intake by the female partner may impair in vivo sperm maturation and possibly fertilization. Moreover, the absence of adverse effect by PPIs on mouse sperm emphasizes the need to develop reprotox assays using human material to better assess the effects of medication intake on sperm physiology.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:To determine the efficacy of pantoprazole therapy for daytime somnolence, psychomotor vigilance, and quality of life in patients with mild-moderate obstructive sleep disordered breathing (OSDB) and gastroesophageal reflux disease (GERD). STUDY DESIGN:Randomized, double-blind, placebo-controlled crossover trial. METHODS:Sixty patients with daytime sleepiness, mild-moderate OSDB and GERD were randomly assigned a 2-week treatment with pantoprazole 40 mg or placebo followed by a 2-week washout period and crossover respectively to 2-week treatment with placebo or pantoprazole. Outcomes included Epworth Sleepiness Score (ESS), sleep-related quality-of-life (FOSQ), and reaction time. RESULTS:With pantoprazole, patients reported statistically significantly greater improvement of overall reflux symptoms (P = 0.0003) and in ESS (P = 0.04). A significant improvement was noted in FOSQ for both treatments with a trend toward greater improvement with pantoprazole (P = 0.058). No improvement in reaction times was observed. CONCLUSION:Patients with coexistent GERD and OSDB noted significant improvement in daytime sleepiness after treatment with pantoprazole over placebo likely related to a reduction in nocturnal reflux-related arousals.

背景与目标：

BACKGROUND & AIMS: :A 42 year old male patient without previous psychiatric history developed 48 hours after he was placed on a helicobacter pylori eradication treatment with amoxicillin, clarithromycin and pantoprazole a brief psychosis accompanied by delusional beliefs, personality changes and disorientation. After discontinuation of the tripletherapie and administration of risperidone he recovered within 72 hours. The follow up of the patient two, twelve and seventy-two weeks after discharge showed that he remained euthymic and free of psychotic symptoms.

背景与目标： : 一名42岁的男性患者在接受阿莫西林，克拉霉素和泮托拉唑根除幽门螺杆菌治疗后48小时出现了精神病，伴有妄想信念，人格改变和迷失方向。停用三联疗法并服用利培酮后，他在72小时内康复。出院后第二，十二和七十二周对患者的随访表明，他仍然保持正常状态，没有精神病症状。

BACKGROUND & AIMS: OBJECTIVE AND DESIGN:The effect of increasing doses of pantoprazole, a newly developed proton pump inhibitor, given at once daily doses of 40, 80 and 120 mg, on intragastric pH and serum gastrin profiles was studied in 15 healthy subjects in a randomized, double-blind, crossover study and compared to recordings without therapy. Measurements of intragastric pH and serum gastrin were performed on the 7th day of treatment by continuous pH recording and radioimmunoassay in blood samples obtained in 1-h intervals, respectively. RESULTS:Pantoprazole significantly increased gastric pH above basal at all pantoprazole doses studied: median 24-h pH rose from 1.2 without therapy to 3.4, 3.3 and 3.6 at 40, 80 and 120 mg daily, respectively. The corresponding integrated 24-h gastrin output was 1632, 2338 and 2248 pg/ml x 24 h compared to 575 pg/ml x 24 h without pantoprazole. There was no interindividual correlation between values of 24-h median pH and 24-h gastrin output at any pantoprazole dose studied. However, fasting gastrin levels closely correlated with 24-h gastrin output (r = 0.789; P < 0.0001). The acid inhibitory effect was significantly (P < 0.01) augmented in Helicobacter pylori positive subjects. CONCLUSION:It is concluded that pantoprazole is an effective inhibitor of gastric acid secretion. Increasing a single pantoprazole dose above 40 mg does not lead to increased median pH elevation. The individual extent of acid inhibition does not predict the magnitude of gastrin elevation. Acid inhibition appears more efficient in Helicobacter pylori positive subjects.

背景与目标：

BACKGROUND & AIMS: Twenty-three healthy, male volunteers completed this doubleblind, randomized, placebo controlled, 2-period crossover study to assess the influence of multiple doses of pantoprazole on single-dose phenytoin pharmacokinetics. During each treatment period, the volunteers received either one 40 mg pantoprazole tablet or placebo for 7 days. In addition, a single-dose of 300 mg (3 x 100 mg capsules) phenytoin sodium was administered on day 4 of each treatment period. A 14-day wash-out period was allowed between phenytoin administrations. The results indicate that pantoprazole neither affects the rate nor the extent of absorption, nor the elimination of phenytoin.

背景与目标： 23名健康的男性志愿者完成了这项双盲，随机，安慰剂对照，2期交叉研究，以评估多剂量泮托拉唑对单剂量苯妥英药代动力学的影响。在每个治疗期间，志愿者接受40 mg泮托拉唑片剂或安慰剂治疗7天。此外，在每个治疗期的第4天给予单剂量的300 mg (3 × 100 mg胶囊) 苯妥英钠。苯妥英钠给药之间允许14天的冲洗期。结果表明，泮托拉唑既不影响吸收速率，也不影响吸收程度，也不影响苯妥英的消除。

BACKGROUND & AIMS: OBJECTIVE:Renal-transplant patients who are immunosuppressed with cyclosporin A (CyA) are often treated with proton-pump inhibitors to prevent ulcer disease. No data are available on the effect of the novel proton-pump inhibitor pantoprazole on CyA levels.

METHODS:In a controlled treatment, we investigated the effect of pantoprazole, which was administered in a pragmatic schedule for acid suppression (40 mg as single oral dose at 2200 hours) in six renal-transplant patients who received CyA (Sandimmun optoral, 50-175 mg twice daily) and prednisolone (5-7.5 mg/24 h). CyA trough levels (0730-0800 hours) were measured by immunoassay.

RESULTS:In the absence of pantoprazole, mean CyA trough levels measured on three consecutive days were between 164 ng/ml and 173 ng/ml (therapeutic range 120-200 ng/ml). Pantoprazole did not affect CyA trough levels during an observation period up to 3 months long.

CONCLUSIONS:Pantoprazole seems to be a safe drug in combination with CyA.

背景与目标： 目的 : 用环孢菌素A (CyA) 免疫抑制的肾移植患者通常接受质子泵抑制剂治疗以预防溃疡病。没有关于新型质子泵抑制剂泮托拉唑对CyA水平的影响的数据。
方法 : 在对照治疗中，我们研究了泮托拉唑的作用，在六名接受CyA (Sandimmun optoral，每天两次50-175 mg) 和泼尼松龙 (5-7.5 mg/24小时) 的肾移植患者中，以实用的方案进行酸抑制 (40 mg，单次口服，2200小时)。通过免疫测定法测量CyA谷水平 (0730-0800小时)。
结果 : 在没有泮托拉唑的情况下，连续三天测量的平均CyA谷水平在164 ng/ml和173 ng/ml之间 (治疗范围120-200 ng/ml)。在长达3个月的观察期内，泮托拉唑不会影响CyA谷水平。
结论 : 泮托拉唑似乎是与CyA联合使用的安全药物。

BACKGROUND & AIMS: OBJECTIVES:To investigate whether pantoprazole (20 mg/d) produces significantly greater symptom control than ranitidine (300 mg/d) in patients with gastro-oesophageal reflux disease (GORD). DESIGN:Multicentre, randomised, double-blind, parallel-group comparison. SETTING:76 general practices in north-west Sydney and Newcastle, New South Wales (Australia), from 19 January 1999 to 22 September 2000. PATIENTS:307 patients aged 18 years or over presenting with symptomatic GORD. INTERVENTIONS:Pantoprazole (20 mg once daily) or ranitidine (150 mg twice daily). MAIN OUTCOME MEASURES:Patient-assessed frequency and severity of heartburn using the Gastrointestinal Symptom Rating Scale (GSRS) and a patient heartburn diary. RESULTS:Pantoprazole was associated with significantly higher rates of complete control of GORD symptoms than ranitidine at four weeks (40% v 19%; P < 0.001), eight weeks (55% v 33%; P < 0.001), six months (71% v 56%; P = 0.007) and 12 months (77% v 59%; P = 0.001). CONCLUSIONS:Low-dose pantoprazole is an effective alternative to standard-dose ranitidine for initial and maintenance treatment of patients with symptomatic GORD.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Stress ulcer prophylaxis (SUP) using ranitidine, a histamine H2 receptor antagonist, has been associated with an increased risk of ventilator-associated pneumonia. The proton pump inhibitor (PPI) pantoprazole is also commonly used for SUP. PPI use has been linked to an increased risk of community-acquired pneumonia. The objective of this study was to determine whether SUP with pantoprazole increases pneumonia risk compared with ranitidine in critically ill patients. METHODS:The cardiothoracic surgery database at our institution was used to identify retrospectively all patients who had received SUP with pantoprazole or ranitidine, without crossover between agents. From January 1, 2004, to March 31, 2007, 887 patients were identified, with 53 patients excluded (pantoprazole, 30 patients; ranitidine, 23 patients). Our analysis compared the incidence of nosocomial pneumonia in 377 patients who received pantoprazole with 457 patients who received ranitidine. RESULTS:Nosocomial pneumonia developed in 35 of the 377 patients (9.3%) who received pantoprazole, compared with 7 of the 457 patients (1.5%) who received ranitidine (odds ratio [OR], 6.6; 95% confidence interval [CI], 2.9 to 14.9). Twenty-three covariates were used to estimate the probability of receiving pantoprazole as measured by propensity score (C-index, 0.77). Using this score, pantoprazole and ranitidine patients were stratified according to their probability of receiving pantoprazole. After propensity adjusted, multivariable logistic regression, pantoprazole treatment was found to be an independent risk factor for nosocomial pneumonia (OR, 2.7; 95% CI, 1.1 to 6.7; p = 0.034). CONCLUSION:The use of pantoprazole for SUP was associated with a higher risk of nosocomial pneumonia compared with ranitidine. This relationship warrants further study in a randomized controlled trial.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Proton pump inhibitors (PPIs) are well established as first-line agents for the treatment of moderate-to-severe gastro-oesophageal reflux disease (GORD). Although all PPIs heal oesophageal lesions and provide symptomatic relief, breakthrough symptoms may occur as acidity levels rebound. Pantoprazole magnesium (pantoprazole-Mg) has a longer elimination half-life than pantoprazole sodium (pantoprazole-Na), resulting in prolonged drug exposure. OBJECTIVE:This study compares the clinical efficacy and safety of once-daily pantoprazole-Mg 40 mg with that of once-daily pantoprazole-Na 40 mg in the management of GORD. METHODS:This was a randomized, double-blind, controlled, multicentre study of non-inferiority design in outpatients with GORD. The study was conducted in 53 centres in Germany from 12 May 2003 to 18 September 2003. Male or female outpatients (aged ≥18 years) with endoscopically confirmed GORD stage I-III (according to the Savary-Miller classification modified by Siewert) were enrolled. Using a computer-generated randomization list, patients were randomized to treatment with pantoprazole-Mg 40 mg plus placebo or pantoprazole-Na 40 mg plus placebo, both given once daily for 4 or 8 weeks depending on healing of oesophagitis. The primary objective was endoscopic healing at 8 weeks. RESULTS:The intent-to-treat (ITT) group consisted of 636 patients (322 receiving pantoprazole-Mg and 314 receiving pantoprazole-Na). Endoscopically confirmed healing of reflux oesophagitis after 8 weeks occurred in 87.3% (95% CI 83.1, 90.7) of patients receiving pantoprazole-Mg and 85.0% (95% CI 80.6, 88.8) of patients receiving pantoprazole-Na (ITT population). The lower bound of the 95% CI for the between-group treatment difference was -1.3, which was within the predefined margin of non-inferiority of -10% to 0%. Healing rates after 4 weeks were superior in the pantoprazole-Mg group (72.7% [95% CI 67.5, 77.5]) compared with the pantoprazole-Na group (66.2% [95% CI 60.7, 71.5]), and the one-sided (lower bound) of the 95% CI for the difference between healing rates for the two treatments was within the predefined non-inferiority margin of -10% to 0%. Both treatments had a similar effect on GORD healing in subgroups of patients based on baseline oesophagitis grade and Helicobacter pylori status. Pantoprazole-Mg had similar efficacy to pantoprazole-Na in relieving a broad range of GORD-related symptoms across the course of the study, although symptomatic relief at 4 weeks was numerically higher in the pantoprazole-Mg group than in the pantoprazole-Na group (statistical analyses were not performed). Both treatments were well tolerated; most adverse events were of mild or moderate severity and unrelated to the study medication, and there were no unexpected safety concerns. CONCLUSION:Pantoprazole-Mg is clinically as effective and well tolerated as pantoprazole-Na in the treatment of GORD stages I-III, demonstrating non-inferiority for oesophageal healing at 8 weeks and superior healing rates at 4 weeks associated with high levels of symptomatic relief.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:The efficacy of pantoprazole as on-demand therapy for the long-term management of patients with mild gastro-oesophageal reflux disease (GORD) has been demonstrated in clinical studies. In this study, the efficacy of pantoprazole 20mg and esomeprazole 20mg as on-demand therapy for relief of symptoms of mild GORD was compared. METHODS:Patients with reflux oesophagitis grade A or B (Los Angeles classification) or endoscopy-negative reflux disease (enGORD) were treated with pantoprazole 20mg once daily for 28 days during the acute phase (AP, n = 236). Patients without heartburn during the final 3 days of the AP entered the long-term phase (LTP, n = 199) and were randomised to either pantoprazole 20mg or esomeprazole 20mg as on-demand treatment for 6 months. Antacids were provided as rescue medication during this phase. The mean intensities of the symptoms of heartburn, acid eructation and pain on swallowing, both separately and as a combined symptom score, together with the mean duration of these symptoms during on-demand treatment, were compared between the two treatment groups. The number of tablets taken was also compared. RESULTS:After 4 weeks of treatment with pantoprazole, 87.3% of patients had relief from heartburn, 74.1% from epigastric pain and 80.8% from acid eructation, according to the investigator assessment. A total of 236 patients were eligible for the on-demand phase. Based on patient diary data, on-demand treatment with pantoprazole resulted in significantly lower mean intensity of heartburn compared with that in the esomeprazole group (1.12 for pantoprazole and 1.32 for esomeprazole, respectively [p = 0.012], in the intention-to-treat [ITT] population). The mean symptom intensities of acid eructation and pain on swallowing, together with the duration of these symptoms, were comparable in the two treatment groups. The combined symptom score of the three symptoms heartburn, acid eructation and pain on swallowing was numerically lower in the pantoprazole group compared with the esomeprazole group (1.72 vs 1.99, respectively, in the ITT population). Tablet intake was comparable in both groups. Relief of symptoms in Helicobacter pylori-positive and -negative patients was also similar in both treatment groups. Both treatments were well tolerated with a good safety profile. CONCLUSION:On-demand therapy with either pantoprazole 20mg or esomeprazole 20mg is a comparably effective treatment strategy for the long-term treatment of non-erosive and mild GORD. However, the mean intensity of heartburn was significantly lower with pantoprazole treatment.

背景与目标：

BACKGROUND & AIMS: :This review summarizes the results of pharmacokinetic and pharmacodynamic drug interaction studies in man with pantoprazole, a new, selective proton pump inhibitor. Various mechanisms have to be considered as causes for potential drug-drug interactions. Proton pump inhibitors (PPIs) in general may alter the absorption of drugs by increasing the intragastric pH. Due to the presence of an imidazole ring, the PPIs of the class of substituted benzimidazole sulfoxides may interfere with the metabolism of other drugs by altering the activity of drug metabolizing enzymes of the cytochrome P450 system, via either induction or inhibition. With the increasing use of PPIs, their interaction potential gains therapeutic importance as was the case with the first and second generation of H2-blockers (cimetidine and ranitidine, respectively). The enhanced selectivity of pantoprazole to the gastric H+/K(+)-ATPase characterizes the new PPI generation. In contrast to omeprazole, pantoprazole has a low potential to interact with the cytochrome P450 system in man. In the drug interaction studies conducted so far, substrates for all relevant cytochrome P450 families involved in the metabolism of drugs in man were investigated. Pantoprazole did not affect the pharmacokinetics or pharmacodynamics of antipyrine, caffeine, carbamazepine, diazepam, diclofenac, digoxin, ethanol, glibenclamide, a hormonal contraceptive (combination of levonorgestrel and ethinylestradiol), metoprolol, nifedipine, phenprocoumon, phenytoin, theophylline and warfarin in man. Pantoprazole also neither induced the metabolism of antipyrine or caffeine, nor increased urinary excretion of the induction markers D-glucaric acid and 6 beta-hydroxycortisol. Vice versa, the investigated drugs had no relevant influence on the pharmacokinetics of pantoprazole.

背景与目标： 这篇综述总结了一种新型选择性质子泵抑制剂泮托拉唑在人体内的药代动力学和药效学药物相互作用研究的结果。必须考虑各种机制作为潜在药物-药物相互作用的原因。质子泵抑制剂 (ppi) 通常可以通过增加胃内ph值来改变药物的吸收。由于存在咪唑环，取代的苯并咪唑亚砜类的ppi可能通过诱导或抑制来改变细胞色素P450系统的药物代谢酶的活性，从而干扰其他药物的代谢。随着ppi的使用增加，它们的相互作用潜力与第一代和第二代H2-blockers (分别为西咪替丁和雷尼替丁) 一样具有治疗重要性。泮托拉唑对胃H/K ()-ATPase的选择性增强是新的PPI世代的特征。与奥美拉唑相反，泮托拉唑与人体细胞色素P450系统相互作用的潜力较低。在迄今为止进行的药物相互作用研究中，研究了参与人体药物代谢的所有相关细胞色素P450家族的底物。泮托拉唑不影响安替比林，咖啡因，卡马西平，地西泮，双氯芬酸，地高辛，乙醇，格列本脲，激素避孕药 (左炔诺孕酮和乙炔雌二醇的组合)，美托洛尔，硝苯地平，苯丙酚，苯妥英，茶碱和华法林人的药代动力学或药效学。泮托拉唑既不诱导安替比林或咖啡因的代谢，也不增加诱导标志物D-葡萄糖酸和6β-羟基皮质醇的尿排泄。反之亦然，所研究的药物对泮托拉唑的药代动力学没有相关影响。

BACKGROUND & AIMS: :Gastro-oesophageal reflux disease (GORD) is associated with a broad array of symptoms that may be typical or atypical of the disease and that may be accompanied by erosive oesophagitis. Symptom scales that have historically been employed to assess response to treatment in GORD clinical trials do not typically account for the heterogeneous, episodic nature of GORD and the poor correlation between patients' and physicians' assessment of symptoms. The ReQuest questionnaire permits self-assessment of changes on a broad range of GORD-related symptoms on a daily basis and in combination with the Los Angeles (LA)-classification (ReQuest/LA-classification) to assess complete remission of GORD. Pantoprazole and esomeprazole are two of the newer proton pump inhibitors and are the first to be systematically reviewed using the ReQuest(trade mark) questionnaire. Results from recent head-to-head trials have shown pantoprazole and esomeprazole to be highly and equally effective treatments for (i) rapid and sustained relief of ReQuest-assessed GORD-related symptoms in patients with non-erosive GORD or endoscopically confirmed erosive GORD, and (ii) achieving a combined outcome comprising endoscopically confirmed healing and ReQuest-assessed symptom relief in patients with erosive GORD. There is some preliminary evidence to suggest that pantoprazole may be the better choice of treatment in terms of its potential to maintain control of symptoms in patients for whom night-time symptoms are a concern and if taken as on-demand rather than continuous maintenance therapy.

背景与目标： : 胃食管反流病 (GORD) 与多种症状有关，这些症状可能是该疾病的典型或非典型症状，并可能伴有糜烂性食管炎。历史上用于评估GORD临床试验对治疗反应的症状量表通常不能解释GORD的异质性，发作性以及患者和医生对症状的评估之间的不良相关性。请求问卷允许每天对广泛的GORD相关症状的变化进行自我评估，并结合洛杉矶 (LA) 分类 (请求/LA-分类) 来评估GORD的完全缓解。泮托拉唑和埃索美拉唑是两种较新的质子泵抑制剂，并且是第一个使用请求 (商标) 问卷进行系统审查的药物。最近的头对头试验的结果表明，泮托拉唑和埃索美拉唑是高度和同等有效的治疗方法，可用于 (i) 快速和持续缓解非糜烂性GORD或经内镜证实的糜烂性GORD患者的请求评估的GORD相关症状，(ii) 在糜烂性GORD患者中实现包括经内窥镜证实的愈合和请求评估的症状缓解的综合结果。有一些初步证据表明，pan托拉唑可能是更好的治疗选择，因为pan托拉唑可以维持夜间症状受到关注的患者的症状控制，并且如果按需而不是连续维持治疗。