BACKGROUND: Proton-pump inhibitors (PPIs) are cornerstone treatments for gastro-esophageal reflux disease (GERD); however, evidence suggests that most patients exhibit partial response to PPIs, suggesting the need for novel therapies that can provide an improved and sustained increase in gastric pH. AIMS: This study aimed to determine the effect of vonoprazan, a novel, orally active small-molecule potassium-competitive acid blocker, versus esomeprazole, a PPI, in preventing heartburn symptoms over a 4-week treatment period in patients with GERD and a partial response to esomeprazole treatment. METHODS: This randomized, double-blind, proof-of-concept, phase 2 clinical trial was conducted between 2016 and 2018 at 39 sites across Europe and designed to evaluate the efficacy and safety of vonoprazan 20 mg once daily (q.d.) and 40 mg q.d. versus esomeprazole 40 mg q.d. after 1:1:1 randomization of symptomatic patients with GERD and a partial response to a healing dose of esomeprazole. RESULTS: Overall, 256 eligible patients (female, 59.4%; mean age, 52.6 years) received vonoprazan 20 mg (n = 85), vonoprazan 40 mg (n = 85), or esomeprazole 40 mg (n = 86); mean (SD) percentages of heartburn-free 24-h periods during double-blind treatment were 36.7% (33.4%), 36.5% (35.6%), and 38.4% (34.8%), respectively, with no intergroup statistical significance. Vonoprazan exposure increased proportionally from the 20-mg to 40-mg dose (mean Cmax : 23.3 ng/ml to 47.1 ng/ml, respectively). Most treatment-emergent adverse events were mild, with no deaths reported. CONCLUSIONS: No statistically significant difference in efficacy and safety was observed among treatment groups, and vonoprazan was well tolerated. The trial is registered with the National Board of Health (EudraCT: 2015-001154-14) database.
- MeSH
- Double-Blind Method MeSH
- Esomeprazole * therapeutic use MeSH
- Gastroesophageal Reflux * drug therapy diagnosis MeSH
- Proton Pump Inhibitors therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Heartburn drug therapy MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase II MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- MeSH
- Amoxicillin administration & dosage therapeutic use MeSH
- Anti-Bacterial Agents MeSH
- Antirheumatic Agents adverse effects MeSH
- Abdominal Pain diagnostic imaging MeSH
- Endoscopy MeSH
- Esomeprazole administration & dosage therapeutic use MeSH
- Helicobacter pylori pathogenicity MeSH
- Clarithromycin administration & dosage therapeutic use MeSH
- Drug Therapy, Combination MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Liver Neoplasms secondary MeSH
- Breast Neoplasms diagnosis drug therapy MeSH
- Peptic Ulcer * diagnosis drug therapy pathology MeSH
- Anti-Ulcer Agents MeSH
- Aged, 80 and over MeSH
- Check Tag
- Humans MeSH
- Aged, 80 and over MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Amoxicillin administration & dosage therapeutic use MeSH
- Anti-Bacterial Agents MeSH
- Antirheumatic Agents adverse effects MeSH
- Abdominal Pain diagnostic imaging MeSH
- Endoscopy MeSH
- Esomeprazole administration & dosage therapeutic use MeSH
- Helicobacter pylori pathogenicity MeSH
- Clarithromycin administration & dosage therapeutic use MeSH
- Drug Therapy, Combination MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Liver Neoplasms secondary MeSH
- Breast Neoplasms diagnosis drug therapy MeSH
- Peptic Ulcer * diagnosis drug therapy pathology MeSH
- Anti-Ulcer Agents MeSH
- Aged, 80 and over MeSH
- Check Tag
- Humans MeSH
- Aged, 80 and over MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Dyspepsia drug therapy MeSH
- Esomeprazole * pharmacokinetics pharmacology therapeutic use MeSH
- Gastroesophageal Reflux drug therapy MeSH
- Drug Evaluation MeSH
- Proton Pump Inhibitors * pharmacokinetics pharmacology therapeutic use MeSH
- Drug Interactions MeSH
- Humans MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Osteoclasts drug effects MeSH
- Peptic Ulcer drug therapy MeSH
- Anti-Ulcer Agents pharmacokinetics pharmacology therapeutic use MeSH
- Stomach Ulcer drug therapy MeSH
- Zollinger-Ellison Syndrome drug therapy MeSH
- Check Tag
- Humans MeSH
Hlavními medikamenty v léčbě acidopeptických onemocnění jsou inhibitory protonové pumpy (IPP). Všechny IPP jsou slabé zásady selektivně se metabolizující v kyselém prostředí a blokující funkci aktivní protonové pumpy. IPP poskytují účinnou léčbu u refluxní nemoci jícnu, eradikace Helicobacter pylori, funkční dyspepsie a gastropatie z nesteroidních antirevmatik. Jsou také součástí léčby u eozinofilní ezofagitidy. IPP první generace zahrnují omeprazol, pantoprazol a lansoprazol, druhé generace esomeprazol a rabeprazol. IPP se liší ve farmakokinetických charakteristikách, tyto rozdíly však nemusí mít klinicky relevantní důsledky. Obecně IPP druhé generace zajišťují rychlejší nástup účinku, protrahovanější inhibici žaludeční sekrece a zejména účinek rabeprazolu je méně závislý na způsobu podávání a méně ovlivňuje funkce cytochromu P450. Účinnost IPP zejména první generace ovlivňuje genetická variabilita enzymu CYP2C19 a je významně nižší u rychlých metabolizátorů. IPP jsou velmi bezpečné a bezprostřední komplikace jsou výjimečné. U helikobakterové infekce vedou k progresi gastrititidy. Přestože způsobují hypergastrinemii, nevykazují IPP maligní potenciál. Jejich dlouhodobé podávání je spojeno s vyšším rizikem fraktur páteře a kyčlí, komunitních pneumonií a klostridiové střevní infekce. Mohou vést ke snížení účinnosti antiagregační léčby s klopidogrelem se zvýšeným rizikem recidivujících kardiovaskulárních příhod, což neplatí pro prasugrel. V nejbližší době nelze očekávat v jiných molekulách či lékových úpravách zásadní pokrok. Příbalové letáky jsou vesměs nevhodně konstruovány a chybí v nich často zásadní informace. Klíčová slova: inhibitory protonové pumpy – omeprazol – lansoprazol – pantoprazol – rabeprazol – esomeprazol – vedlejší účinky – interakce
Proton pump inhibitors (PPI) are the primary medication in the treatment of acid-related diseases. All proton pump inhibitors are weak bases selectively metabolised in an acid environment which block the function of active proton pumps. Proton pump inhibitors provide efficient treatment for gastroesophageal reflux disease, Helicobacter pylori, functional dyspepsia and NSAID gastropathy. PPI may be helpful in patients with eosinophilic oesophagitis. PPI of the first generation comprise omeprazole, pantoprazole and lansoprazole, the second one is represented by esomeprazole and rabeprazole. Proton pump inhibitors differ in pharmacokinetic properties but these differences do not necessarily have clinically relevant consequences. Generally, second generation proton pump inhibitors provide a faster onset of effect, longer gastric secretion inhibition, and specifically the effect of rabeprazole is less dependent on the method of administration and has less influence on the function of cytochrome P450. The effect of proton pump inhibitors, particularly the first generation, is modified by the genetic variety of the CYP2C19 enzyme and is significantly lower in rapid metabolisers. Proton pump inhibitors are very safe and immediate complications are rare. They can cause progression of gastritis in Helicobacter infection. In spite of causing hypergastrinemia, they do not have malignant potential. Their long-term administration is associated with an increased risk of pelvis and hip fractures, community-acquired pneumonia, and clostridium infection. They decrease the effect of antiaggregant therapy with clopidogrel, and increase the risk of recurrent cardiovascular events. This effect is not proven in prasugrel. We cannot expect any potential progression in developing new molecules or PPI formulas. The instructions for patients are usually not clearly presented and often lack important information. Keywords: proton pump inhibitors – omeprazole – lansoprazole – pantoprazole – rabeprazole – esomeprazole – side effects – interactions
- MeSH
- 2-Pyridinylmethylsulfinylbenzimidazoles pharmacology adverse effects therapeutic use MeSH
- Anti-Inflammatory Agents, Non-Steroidal adverse effects MeSH
- Cytochrome P-450 CYP2C19 genetics MeSH
- Eosinophilic Esophagitis drug therapy MeSH
- Esomeprazole pharmacology adverse effects therapeutic use MeSH
- Fractures, Bone chemically induced MeSH
- Gastroesophageal Reflux drug therapy MeSH
- Helicobacter Infections drug therapy MeSH
- Proton Pump Inhibitors * pharmacology adverse effects therapeutic use MeSH
- Clostridium Infections chemically induced MeSH
- Lansoprazole pharmacology adverse effects therapeutic use MeSH
- Drug Interactions MeSH
- Humans MeSH
- Misoprostol therapeutic use MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Omeprazole pharmacology adverse effects therapeutic use MeSH
- Pantoprazole MeSH
- Anti-Ulcer Agents pharmacology adverse effects therapeutic use MeSH
- Rabeprazole pharmacology adverse effects therapeutic use MeSH
- Stomach Ulcer drug therapy chemically induced prevention & control MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- MeSH
- Histamine H2 Antagonists * adverse effects therapeutic use MeSH
- Child MeSH
- Esomeprazole administration & dosage MeSH
- Gastroesophageal Reflux * drug therapy MeSH
- Proton Pump Inhibitors * administration & dosage adverse effects therapeutic use MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Publication type
- Practice Guideline MeSH
Idiopatická plicní fibróza (IPF) je difuzní primárně fibrotizující plicní proces nejasné etiologie. Do roku 2011 byla IPF neléčitelná, tzn. že žádné léčebné postupy do té doby používané nebyly efektivní na základě medicíny založené na důkazech. Přelom v léčbě nastal po zavedení pirfenidonu do léčebné praxe IPF. V ČR byl tento lék dostupný již od roku 2011 v tzv. programu na jméno pacienta, pak od roku 2012 po registraci přípravku v zemích EU bylo možné lék pro pacienty s IPF získat na tzv. mimořádný dovoz. Od 1. 7. 2014 je pirfenidon (ESBRIET, Roche) hrazen z prostředků zdravotního pojištění. Pirfenidonem byla odstartována nová éra pro pacienty s IPF i pro jejich lékaře. Krom tohoto léku se dostává na trh v rámci EU další antifibrotický lék, a to nintedanib (OFEV, Boehringer-Ingelheim). Je velmi pravděpodobné, že do léčby IPF v nejbližší době zasáhnou i jiné léky, ovlivňující fibroproliferaci, léčba IPF tedy bude skýtat širokou škálu fenotypově specifických léčeb včetně kombinované léčby. My všichni, kdo pacienty s IPF léčíme, se na to již velmi těšíme.
Idiopathic pulmonary fibrosis (IPF) is a diffuse primarily fibrosing lung disease of unknown origin. Until 2011 IPF was considered untreatable, i.e. the currently used treatment modalities did not show any effectivity from the point of view of evidence-based medicine. The introduction of pirfenidone counted for the milestone in the treatment of IPF. In the Czech republic this drug was available from autumn 2011 by means of so called named-patient programme and since 2012 after a registration in EU pirfenidone was available in the Czech republic via extraordinary reimbursement of imported drug. Since 1st July 2014 is pirfenidone (ESBRIET, Roche) regularly reimbursed by healthcare insurance funds. Pirfenidone started new era for patients with IPF and for their physicians as well. Aside this drug a new antifibrotic agent, nintedanib, is emerging on EU market (OFEV, Boehringer-Ingelheim). It is highly probably that in a near future more drugs influencing mechanisms of fibroproliferation will appear and IPF treatment options will offer a wide scale o phenotype- specific treatment modialities, combined treatment included. All of us who care for IPF patients look for that with a hope.
- MeSH
- Acetylcysteine administration & dosage adverse effects therapeutic use MeSH
- Diagnostic Techniques, Respiratory System * utilization MeSH
- Esomeprazole administration & dosage adverse effects therapeutic use MeSH
- Drug Therapy * methods trends utilization MeSH
- Idiopathic Pulmonary Fibrosis * drug therapy therapy MeSH
- Indoles administration & dosage adverse effects therapeutic use MeSH
- Disease Attributes MeSH
- Humans MeSH
- Opioid Peptides therapeutic use MeSH
- Oxygen Inhalation Therapy methods utilization MeSH
- Pyridones administration & dosage adverse effects therapeutic use MeSH
- Lung Transplantation methods utilization MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- Geographicals
- Czech Republic MeSH
Idiopatická plicní fibróza (IPF) je difuzní primárně fibrotizující plicní proces nejasné etiologie. Do roku 2011 byla IPF neléčitelná, tzn. že žádné léčebné postupy do té doby používané nebyly efektivní na základě medicíny založené na důkazech. Přelom v léčbě nastal po zavedení pirfenidonu do léčebné praxe IPF. V ČR byl tento lék dostupný již od roku 2011 v tzv. programu na jméno pacienta, pak od roku 2012 po registraci přípravku v zemích EU bylo možné lék pro pacienty s IPF získat na tzv. mimořádný dovoz. Od 1. 7. 2014 je pirfenidon (ESBRIET, Roche) hrazen z prostředků zdravotního pojištění. Pirfenidonem byla odstartována nová éra pro pacienty s IPF i pro jejich lékaře. Krom tohoto léku se dostává na trh v rámci EU další antifibrotický lék, a to nintedanib (OFEV, Boehringer-Ingelheim). Je velmi pravděpodobné, že do léčby IPF v nejbližší době zasáhnou i jiné léky, ovlivňující fibroproliferaci, léčba IPF tedy bude skýtat širokou škálu fenotypově specifických léčeb včetně kombinované léčby. My všichni, kdo pacienty s IPF léčíme, se na to již velmi těšíme.
Idiopathic pulmonary fibrosis (IPF) is a diffuse primarily fibrosing lung disease of unknown origin. Until 2011 IPF was considered untreatable, i.e. the currently used treatment modalities did not show any effectivity from the point of view of evidence-based medicine. The introduction of pirfenidone counted for the milestone in the treatment of IPF. In the Czech republic this drug was available from autumn 2011 by means of so called named-patient programme and since 2012 after a registration in EU pirfenidone was available in the Czech republic via extraordinary reimbursement of imported drug. Since 1st July 2014 is pirfenidone (ESBRIET, Roche) regularly reimbursed by healthcare insurance funds. Pirfenidone started new era for patients with IPF and for their physicians as well. Aside this drug a new antifibrotic agent, nintedanib, is emerging on EU market (OFEV, Boehringer-Ingelheim). It is highly probably that in a near future more drugs influencing mechanisms of fibroproliferation will appear and IPF treatment options will offer a wide scale o phenotype- specific treatment modialities, combined treatment included. All of us who care for IPF patients look for that with a hope.
- MeSH
- Acetylcysteine administration & dosage adverse effects therapeutic use MeSH
- Diagnostic Techniques, Respiratory System * utilization MeSH
- Esomeprazole administration & dosage adverse effects therapeutic use MeSH
- Drug Therapy * methods trends utilization MeSH
- Idiopathic Pulmonary Fibrosis * drug therapy therapy MeSH
- Indoles administration & dosage adverse effects therapeutic use MeSH
- Disease Attributes MeSH
- Humans MeSH
- Opioid Peptides therapeutic use MeSH
- Oxygen Inhalation Therapy methods utilization MeSH
- Pyridones administration & dosage adverse effects therapeutic use MeSH
- Lung Transplantation methods utilization MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- Geographicals
- Czech Republic MeSH
Hlavními medikamenty v léčbě acidopeptických onemocnění jsou inhibitory protonové pumpy (IPP). Všechny IPP jsou slabé zásady selektivně se metabolizující v kyselém prostředí a blokující funkci aktivní protonové pumpy. IPP poskytují účinnou léčbu u refluxní nemoci jícnu, eradikace Helicobacter pylori, funkční dyspepsie a gastropatie z nesteroidních antirevmatik. IPP se liší ve farmakokinetických charakteristikách, tyto rozdíly však nemusí mít klinicky relevantní důsledky. Účinnost IPP zejména první generace ovlivňuje genetická variabilita enzymu CYP2C19 a je významně nižší u rychlých metabolizátorů. IPP jsou velmi bezpečné a bezprostřední komplikace jsou výjimečné. U helikobakterové infekce vedou k progresi gastritidy. Přes hypergastrinemii nemají IPP maligní potenciál. Jejich dlouhodobé podávání je spojeno s vyšším rizikem fraktur páteře a kyčlí, komunitních pneumonií a klostridiové střevní infekce. Mohou vést ke snížení účinnosti antiagregační léčby s klopidogrelem se zvýšeným rizikem recidivujících kardiovaskulárních příhod. Příbalové letáky jsou vesměs nevhodně konstruovány a chybí v nich často zásadní informace.
Proton pump inhibitors are the most important medicines in the treatment of acid related diseases. All proton pump inhibitors are weak bases being selectively metabolised in the acid environment and blocking the function of active proton pumps. Proton pump inhibitors provide efficient treatment for gastroesophageal reflux disease, Helicobacter pylori eradication, functional dyspepsia and NSAID gastropathy. Proton pump inhibitors differ in pharmacokinetc properties but these differences do not necessarily have clinically relevant consequences. Generally, 2nd generation proton pump inhibitors provide faster onset of effect, longer gastric secretion inhibition, and specifically the effect of rabeprazole is less dependent on the method of administration and has less influence on the function of the cytochrome P450. The main effect of the 1st generation proton pump inhibitors is modified by the genetic variety of the enzyme CYP2C19 and it is significantly lower in rapid metabolizers. Proton pump inhibitors are very safe and immediate complications are exceptional. They can cause progression of gastritis in Helicobacter infection. In spite of hypergastrinemia they do not have malignant potential. Their long-lasting usage is associated with an increased risk of pelvis and hip fractures, community pneumonia, and clostridium infection. They decrease the effect of antiaggregant therapy with clopidogrel, and increase the risk of recurrent cardiovascular events. The instructions for patients are clearly presented and often important information is lacking. Key words: proton pump inhibitors – omeprazole – lansoprazole – pantoprazole – rabeprazole – esomeprazole – side effects – interactions The author declares he has no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers. Submitted: 25. 7. 2013 Accepted: 12. 8. 2013
- MeSH
- Bacterial Infections MeSH
- Esomeprazole MeSH
- Gastrins drug effects MeSH
- Gastritis MeSH
- Helicobacter pylori drug effects MeSH
- Platelet Aggregation Inhibitors MeSH
- Proton Pump Inhibitors * pharmacology classification adverse effects therapeutic use MeSH
- Clinical Trials as Topic MeSH
- Lansoprazole MeSH
- Drug Interactions * MeSH
- Humans MeSH
- Meta-Analysis as Topic MeSH
- Intestinal Diseases MeSH
- Omeprazole pharmacology MeSH
- Pantoprazole MeSH
- Pneumonia etiology MeSH
- Rabeprazole MeSH
- Randomized Controlled Trials as Topic MeSH
- Practice Guidelines as Topic MeSH
- Cytochrome P-450 Enzyme System genetics MeSH
- Iron MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
