Proton pump inhibitors (PPIs) were clinically introduced more than 25 years ago and have since proven to be invaluable, safe, and effective agents for the management of a variety of acid-related disorders. Although all members in this class act in a similar fashion, inhibiting active parietal cell acid secretion, there are slight differences among PPIs relating to their pharmacokinetic properties, metabolism, and Food and Drug Administration (FDA)-approved clinical indications. Nevertheless, each is effective in managing gastroesophageal reflux disease and uncomplicated or complicated peptic ulcer disease. Despite their overall efficacy, PPIs do have some limitations related to their short plasma half-lives and requirement for meal-associated dosing, which can lead to breakthrough symptoms in some individuals, especially at night. Longer-acting PPIs and technology to prolong conventional PPI activity have been developed to specifically address these limitations and may improve clinical outcomes.
Gastroesophageal Reflux ; Metabolism ; Peptic Ulcer ; Pharmacokinetics ; Plasma ; Proton Pump Inhibitors* ; Proton Pumps* ; Protons* ; Rabeprazole ; United States Food and Drug Administration

This work aimed to set up a high performance liquid chromatography (HPLC) method to determine the concentration of lansoprazole in human plasma and study the pharmacokinetic characters of lansoprazole in Chinese healthy volunteers after intravenous (IV) infusion. In accordance with double 3 x 3 Latin square design with self-crossover design, 12 volunteers were randomly divided into six groups, with half males and half females. The volunteers were administered with single dose of 15, 30, 60 mg of lansoprazole by IV infusion at a constant speed respectively, to study the clinical pharmacokinetics of lansoprazole. The linear range of lansoprazole in human plasma was 0.020-4.970 microg/ml (r = 0.9999); The intra-day and inter-day RSD were less than 10%. After receiving single doses of 15, 30 and 60 mg of lansoprazole, t(1/2) were (1.663 +/- 0.405) h, (1.541 +/- 0.339)h and (1.747 +/- 0.156) h; Cmax were (1.065 +/- 0.094) microg/ml, (2.104 +/- 0.312) microg/ml and (3.786 +/- 0.356) microg/ml; AUC(0-infinity) were (2.376 +/- 0. 432) microg x h/ ml, (4.722 +/- 0.753) microg x h/ml and (10.495 +/- 2.129) microg x h/ml respectively. The improved HPLC method is simple, rapid and reproducible. It could be used for determination of the concentration of lansoprazole in human plasma. The pharmacokinetics of lansoprazole for injection was found to fit the linear dynamics in vivo within the dose range of 15 to 60 mg. In addition, the results suggested that gender had no statistic significant effect on the pharmacokinetic process of lansoprazole after IV infusion of single dose.
2-Pyridinylmethylsulfinylbenzimidazoles ; administration & dosage ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Female ; Humans ; Infusions, Intravenous ; Lansoprazole ; Male ; Proton Pump Inhibitors

OBJECTIVEHelicobacter pylori (H. pylori) eradication remains a challenge with increasing antibiotic resistance. Hybrid therapy has attracted widespread attention because of initial report with good efficacy and safety. However, many issues on hybrid therapy are still unclear such as the eradication efficacy, safety, compliance, influencing factors, correlation with antibiotic resistance, and comparison with other regimens. Therefore, a comprehensive review on the evidence of hybrid therapy for H. pylori infection was conducted.

DATA SOURCESThe data used in this review were mainly from PubMed articles published in English up to September 30, 2015, searching by the terms of "Helicobacter pylori" or "H. pylori", and "hybrid".

STUDY SELECTIONClinical research articles were selected mainly according to their level of relevance to this topic.

RESULTSTotally, 1871 patients of 12 studies received hybrid therapy. The eradication rates were 77.6-97.4% in intention-to-treat and 82.6-99.1% in per-protocol analyses. Compliance was 93.3-100.0%, overall adverse effects rate was 14.5-67.5%, and discontinued medication rate due to adverse effects was 0-6.7%. H. pylori culture and sensitivity test were performed only in 13.3% patients. Pooled analysis showed that the eradication rates with dual clarithromycin and metronidazole susceptible, isolated metronidazole or clarithromycin resistance, and dual clarithromycin and metronidazole resistance were 98.5%, 97.6%, 92.9%, and 80.0%, respectively. Overall, the efficacy, compliance, and safety of hybrid therapy were similar with sequential or concomitant therapy. However, hybrid therapy might be superior to sequential therapy in Asians.

CONCLUSIONSHybrid therapy showed wide differences in the efficacy but consistently good compliance and safety across different regions. Dual clarithromycin and metronidazole resistance were the key factor to efficacy. Hybrid therapy was similar to sequential or concomitant therapy in the efficacy, safety, and compliance.

Clarithromycin ; administration & dosage ; adverse effects ; Drug Resistance, Bacterial ; Drug Therapy, Combination ; Helicobacter pylori ; drug effects ; Humans ; Medication Adherence ; Metronidazole ; administration & dosage ; adverse effects ; Proton Pump Inhibitors ; administration & dosage

BACKGROUND/AIMS: The effects of Histamine-2 receptor antagonists and proton pump inhibitors on the gastrointestinal motility have not yet been sufficiently investigated. The aim of this study was to determine the effects of intravenous bolus administration of famotidine and omeprazole on the rate of gastric emptying using the continuous 13C breath test (BreathID system, Exalenz Bioscience Ltd, Israel). METHODS: Twelve healthy male volunteers participated in this randomized, 3-way crossover study. After fasting overnight, the subjects were randomly assigned to receive 20 mg of famotidine, 20 mg of omeprazole or 20 mL of saline alone by intravenous bolus injection before a test meal (200 kcal per 200 mL, containing 100 mg of 13C-acetate). Gastric emptying was monitored for 4 hours after the ingestion of test meal by the 13C-acetic acid breath test performed using the BreathID system. RESULTS: No significant differences in the calculated parameters, namely, the T1/2, Tlag, GEC, beta and kappa, were observed among the 3 test conditions. CONCLUSIONS: The study revealed that intravenous administration of gastric acid suppressant drugs had no significant influence on the rate of gastric emptying in comparison with that of saline alone as a placebo. Our results indicating the absence of any effect of either famotidine or omeprazole on accelerating the rate of gastric emptying suggest that both medications can be administered safely to patients suffering from hemorrhagic peptic ulcers who need to be kept nil by mouth from the viewpoint of possible acceleration of gastrointestinal motility in the clinical setting.
Acceleration ; Administration, Intravenous ; Breath Tests ; Cross-Over Studies ; Eating ; Famotidine ; Fasting ; Gastric Acid ; Gastric Emptying ; Gastrointestinal Motility ; Humans ; Male ; Meals ; Mouth ; Omeprazole ; Peptic Ulcer ; Proton Pump Inhibitors ; Proton Pumps ; Protons ; Stress, Psychological

OBJECTIVE: To observe the clinical efficacy of sequential therapy with pantoprazole in patients with gastro esophageal reflux disease (GERD). METHODS: A total of 80 patients with GERD were double-blindedly randomized into 2 groups: 40 patients received sequential therapy with pantoprazole 40 mg injection, twice daily for 2 weeks, and then pantoprazole 40 mg oral administration,twice daily for 2 weeks; the other 40 patients received pantoprazole 40 mg oral administration alone,twice daily for 4 weeks. Doctors and patients recorded the severity and frequency of heartburn before and during the treatment. The curative effects of the 2 groups were compared. RESULTS: The total effective rate in the sequential therapy group was higher than that of the oral administration group(95.0% vs 77.5%, P<0.05). CONCLUSION Pantoprazole sequential therapy is effective for GERD.
2-Pyridinylmethylsulfinylbenzimidazoles ; administration & dosage ; therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Female ; Gastroesophageal Reflux ; drug therapy ; Humans ; Male ; Middle Aged ; Pantoprazole ; Proton Pump Inhibitors ; administration & dosage ; therapeutic use

This study is to prepare the pantoprazole sodium enteric-coated tablet which is compacted by pellets. The enteric-coated pantoprazole sodium pellets were prepared by fluid bed coating technology. The pantoprazole sodium enteric-coated tablets were prepared by direct compression of the enteric-coated pellets and suitable excipients. In vitro dissolution method and scanning electron microscope method were used for the observation of the drug release behavior before and after compression of the pellets. The optimized formulation is: the coating level is 55%, the plasticizer content is 20%, the ratio of Eudragit L30D-55/NE30D is 8 : 2, enteric-coated pellets/excipients (MCC/PPVP/PEG 6000 = 2 : 1 : 1) is 5 : 5, the enteric-coated tablets release in artificial gastric fluid in 2 h is less than 10%, while in artificial intestinal fluid in 1 h is more than 85%. The release behavior of pantoprazole sodium enteric-coated pellets-type tablet is quite well. And it may be used in industrial production.
2-Pyridinylmethylsulfinylbenzimidazoles ; administration & dosage ; chemistry ; Chromatography, High Pressure Liquid ; methods ; Drug Carriers ; Drug Compounding ; methods ; Excipients ; Microscopy, Electron, Scanning ; Plasticizers ; chemistry ; Polyethylene Glycols ; chemistry ; Polymethacrylic Acids ; chemistry ; Proton Pump Inhibitors ; administration & dosage ; chemistry ; Solubility ; Tablets, Enteric-Coated ; chemistry ; Technology, Pharmaceutical

BACKGROUND/AIMS: Bismuth-containing quadruple and moxifloxacin-based triple regimens are recommended as second-line therapy for Helicobacter pylori infection. The aim of this study was to compare the efficacy of each regimen. METHODS: From August 2004 to October 2012, a total of 949 patients (mean age, 54.32+/-12.08 years; male, 49.4%) who failed H. pylori eradication with a standard triple regimen were included. Patients treated with a bismuth-containing quadruple regimen for 7 and 14 days were designated as 7-BMT and 14-BMT, respectively, and those treated with a moxifloxacin-based triple regimen for 7 and 14 days were designated as 7-MA and 14-MA, respectively. H. pylori eradication was confirmed using the 13C-urea breath test, rapid urease test or histology. RESULTS: The eradication rates by 7-BMT, 14-BMT, 7-MA, and 14-MA were 66.4% (290/437), 71.1% (113/159), 53.1% (51/96), and 73.5% (189/257), respectively, by intention-to-treat analysis (ITT) and 76.5% (284/371), 83.8% (109/130), 55.6% (50/90), and 80.6% (187/232), respectively, by per-protocol analysis (PP). The eradication rates were higher in 14-BMT than 7-BMT by the ITT and PP analyses (p=0.277 and p=0.082, respectively). The 14-BMT and 14-MA treatments showed similar efficacies by ITT and PP (p=0.583 and p=0.443, respectively). CONCLUSIONS: The 7-BMT, 14-BMT, and 14-MA treatments showed similar and suboptimal efficacies. In both regimens, extending the duration of treatment may be reasonable considering the high level of antibiotic resistance in Korea.
Adult ; Aged ; Amoxicillin/administration & dosage ; Antacids/*administration & dosage ; Anti-Infective Agents/*administration & dosage ; Bismuth/*administration & dosage ; Drug Administration Schedule ; Drug Therapy, Combination/methods ; Female ; Fluoroquinolones/*administration & dosage ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Intention to Treat Analysis ; Male ; Metronidazole/administration & dosage ; Middle Aged ; Proton Pump Inhibitors/administration & dosage ; Retrospective Studies ; Tetracycline/administration & dosage ; Treatment Outcome

BACKGROUNE/AIMS: Esophageal variceal ligation (EVL) is the most preferable method for controling variceal bleeding. However, EVL is associated with complications such as hemorrhage, chest pain, dysphagia, and odynophagia due to post-EVL ulcers in the esophageal mucosa. The aim of this study was to assess the effect of proton pump inhibitor (PPI), pantoprazole on the healing of post-EVL ulcers. METHODS: Forty seven patients were randomly allocated into PPI group and control group. Patients in PPI group received 40 mg of pantoprazole intravenously for 3 days after EVL, then 40 mg of oral pantoprazole for 11 days consecutively. Control patients received intravenous and oral placebo. Endoscopic examinations were performed twice at 7+/-2 days and 14+/-2 days after EVL respectively. Clinical outcomes include the size of ulcers, symptoms reported by patients; chest pain, dysphagia, and odynophagia. RESULTS: Forty seven patients completed the 7 days protocol (PPI/control; 25/22), and twenty six patients completed the 14 days protocol (PPI/control; 16/10). Post-EVL ulcers in PPI group were significantly smaller than those in control group (7 days; 98.7 mm2/119.4 mm2, 14 days; 32.3 mm2/43.8 mm2, p<0.01). No difference was observed between two the groups with respect to summations of symptom scores (p>0.05). Nineteen patients (PPI/control; 9/10) did not complete the 14 days protocol due to patients' refusal and adverse outcomes, such as hepatic failure and sepsis with bleeding from post-EVL ulcer occurred in two patients of control group. CONCLUSIONS: PPI treatment following EVL may be effective in healing post-EVL ulcer.
2-Pyridinylmethylsulfinylbenzimidazoles/administration & dosage/*therapeutic use ; Anti-Ulcer Agents/administration & dosage/*therapeutic use ; Esophageal and Gastric Varices/complications/*surgery ; Esophagoscopy ; Female ; Gastrointestinal Hemorrhage/prevention & control ; Humans ; Ligation ; Male ; Middle Aged ; Proton Pump Inhibitors/administration & dosage/*therapeutic use ; Regression Analysis ; Sickness Impact Profile ; Ulcer/*drug therapy/etiology

INTRODUCTIONThere are growing concerns that the use of proton pump inhibitors (PPIs) may be inappropriate in instances that do not conform to evidence-based indications. This point-prevalence study aimed to investigate the frequency, indications and appropriateness of use of PPIs in hospitalised patients on a randomly chosen day.

METHODSOn a randomly chosen day, all inpatients were documented, and those on any form of PPIs on that day were determined. Indications for maintaining these patients on PPIs were obtained from the electronic medical records, which were then recorded and cross-referenced against a list of accepted indications adapted from the US Food and Drug Administration (FDA)-approved list.

RESULTSIn all, 1,025 inpatients were documented. Of the 477 (46.5%) inpatients using PPIs, only 219 (45.9%) fulfilled the FDA-approved indications, while the majority (n = 258, 54.1%) did not. Overall, PPIs were not strictly indicated for use in 206 (43.2%) inpatients, according to FDA criteria. Of the 477 inpatients on PPIs, 52 (10.9%) had borderline indications based on expert consensus/guidelines other than FDA criteria.

CONCLUSIONAlthough the use of PPIs is prevalent in hospitals, less than half of the hospitalised patients using PPIs in our study had evidence-based indications that supported such use. The overuse of PPIs has a negative impact on healthcare costs and may lead to adverse effects. Steps to curb the inappropriate use of PPIs should address factors such as indications for the initiation of PPIs, and reassessment of the need for ongoing PPI use in inpatients upon discharge and during outpatient reviews.

Anemia ; drug therapy ; Dyspepsia ; drug therapy ; Electronic Health Records ; Hospitalization ; Humans ; Inappropriate Prescribing ; statistics & numerical data ; Platelet Aggregation Inhibitors ; therapeutic use ; Practice Guidelines as Topic ; Prevalence ; Proton Pump Inhibitors ; therapeutic use ; Retrospective Studies ; Singapore ; Stomach Diseases ; drug therapy ; United States ; United States Food and Drug Administration

BACKGROUND/AIMS: Conflicting results have been reported whether patients with non-ulcer dyspepsia (NUD) respond differently to Helicobacter pylori (H. pylori) eradication treatment compared with patients with peptic ulcer diseases (PUD). The aim of this study was to evaluate any difference in H. pylori eradication rates between patients with NUD and PUD according to each proton pump inhibitor (PPI). METHODS: From September, 2004 to April, 2007, we retrospectively reviewed 2,297 patients with NUD (1,050 patients) or PUD (1,247 patients) infected with H. pylori. All patients received a standard 1 week triple therapy comprising of one of the five PPIs (pantoprazole, esomeprazole, omeprazole, lansoprazole, rabeprazole), clarithromycin and amoxicillin. The follow-up H. pylori test was performed 4 weeks after the completion of therapy. RESULTS: There was no significant difference in the eradication rates between the two groups. In comparison of eradication rates according to PPI, omeprazole- based triple therapy group showed higher eradication rate than other groups in patients with NUD, but not in patients with PUD. CONCLUSIONS: This study failed to show any difference in H. pylori eradication rate between patients with NUD and PUD. There is no convincing evidence that the eradication rate may be affected by different PPI.
2-Pyridinylmethylsulfinylbenzimidazoles/therapeutic use ; Adult ; Amoxicillin/administration & dosage ; Anti-Bacterial Agents/administration & dosage ; Anti-Ulcer Agents/administration & dosage ; Clarithromycin/administration & dosage ; Data Interpretation, Statistical ; Drug Therapy, Combination ; Dyspepsia/*drug therapy/etiology/microbiology ; Enzyme Inhibitors/therapeutic use ; Female ; Helicobacter Infections/complications/*drug therapy/microbiology ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Omeprazole/analogs & derivatives/therapeutic use ; Peptic Ulcer/*drug therapy/etiology/microbiology ; Proton Pump Inhibitors/therapeutic use