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International Journal of Molecular... Sep 2022Proton pump inhibitors (PPIs) are an antacid drug often used in acid-related disorders. They decrease acid secretion in the stomach by blocking an enzyme called H+/K+... (Review)
Review
Proton pump inhibitors (PPIs) are an antacid drug often used in acid-related disorders. They decrease acid secretion in the stomach by blocking an enzyme called H+/K+ ATPase which controls acid production. Introduced to the market in 1989, their use has increased rapidly worldwide and they are now among the top 10 most prescribed drugs in the United States. As of 2015, the FDA has already approved six drugs of this class (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole and rabeprazole). Recently, the risks and benefits of long-term PPI use were questioned and many studies indicated that their use should be carefully considered, especially in young patients, whose treatment with these drugs could last many years. Even greater concerns have been raised about a potential positive association between PPIs and osteoporotic fracture risk including the hip, spine and wrist. Although based on observational studies, there is substantial evidence associating the long-term use of PPIs and fracture. This relationship is only partially admitted due to the lack of consistent effects of PPIs on bone mineral density loss. Therefore, this narrative review aimed to discuss the recent findings pertaining to the risk of osteoporotic fracture associated with PPIs, in particular prolonged use, and to call for further research to elucidate the mechanisms associated with this bone fragility.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adenosine Triphosphatases; Antacids; Bone Density; Dexlansoprazole; Esomeprazole; Humans; Lansoprazole; Omeprazole; Osteoporotic Fractures; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; United States
PubMed: 36142643
DOI: 10.3390/ijms231810733 -
Frontiers in Pharmacology 2022Proton pump inhibitors (PPIs) are among the most prescribed drugs worldwide and include omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole. Their use... (Review)
Review
Proton pump inhibitors (PPIs) are among the most prescribed drugs worldwide and include omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole. Their use in pediatrics is approved for children older than 1 year, for the short-term treatment of symptomatic gastroesophageal reflux disease (GERD), healing of erosive esophagitis, treatment of peptic ulcer disease, and eradication of . PPIs are also considered the standard of care for pediatric eosinophilic esophagitis. Despite the strict range of indications, the use of this class of molecules has increased in all pediatric age ranges. The long-term gastric acid suppression in children has been linked to increased risks of gastrointestinal and lower respiratory tract infections, bone fractures, and allergy. This study aims to provide a comprehensive overview of the mechanism of actions, use (and misuse) in infants and children, and safety of PPIs.
PubMed: 35222047
DOI: 10.3389/fphar.2022.839972 -
BMC Pharmacology & Toxicology Jul 2020The pharmacokinetics of proton pump inhibitors (PPIs) may be affected by food intake. We aimed to evaluate the effect of food on the pharmacokinetics of omeprazole,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The pharmacokinetics of proton pump inhibitors (PPIs) may be affected by food intake. We aimed to evaluate the effect of food on the pharmacokinetics of omeprazole, rabeprazole, and pantoprazole.
SETTING
The study population comprised 186 healthy volunteers participating in 6 bioequivalence clinical trials.
METHOD
Subjects were evaluated to determine the effect of a high-fat breakfast on the pharmacokinetics of omeprazole (n = 36), rabeprazole (n = 69), and pantoprazole (n = 81).
MAIN OUTCOME MEASURE
Drug plasma concentrations were measured using high-performance liquid chromatography coupled to mass spectrometry.
RESULTS
Food affected the pharmacokinetics of omeprazole (increased T and decreased AUC and C), pantoprazole (increased T and decreased AUC), and rabeprazole (increased T, C and half-life). Food increased variability in T for all 3 drugs, delaying absorption around 3 to 4 h and until 20 h in some subjects.
CONCLUSION
As food delays the absorption of PPIs and increases their variability, it would be better to administer these drugs under fasting conditions.
TRIAL REGISTRATION
European Union Drug Regulating Authorities Clinical Trials Database: EudraCT : 2004-003863-59 (registration date 05/MAR/2004), EudraCT 2006-001162-17 (registration date 17-MAR-2006), EudraCT: 2007-002489-37 (registration date 12-JUN-2007), EudraCT: 2007-002490-31 (registration date 12-JUN-2007), EudraCT: 2010-024029-19 (registration date 23-NOV-2010).
Topics: Adult; Anti-Ulcer Agents; Cross-Over Studies; Cytochrome P-450 CYP2C19; Dietary Fats; Fasting; Female; Food-Drug Interactions; Genotype; Humans; Male; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Young Adult
PubMed: 32711578
DOI: 10.1186/s40360-020-00433-2 -
JAMA Pediatrics Apr 2021The use of proton pump inhibitors (PPIs) in children has increased substantially in recent years, concurrently with emerging concerns that these drugs may increase the... (Observational Study)
Observational Study
IMPORTANCE
The use of proton pump inhibitors (PPIs) in children has increased substantially in recent years, concurrently with emerging concerns that these drugs may increase the risk of asthma. Whether PPI use in the broad pediatric population is associated with increased risk of asthma is not known.
OBJECTIVE
To investigate the association between PPI use and risk of asthma in children.
DESIGN, SETTING, AND PARTICIPANTS
This nationwide cohort study collected registry data in Sweden from January 1, 2007, to December 31, 2016. Children and adolescents 17 years or younger were matched by age and propensity score into 80 870 pairs of those who initiated PPI use and those who did not. Data were analyzed from February 1 to September 1, 2020.
EXPOSURES
Initiation of PPI use.
MAIN OUTCOMES AND MEASURES
The primary analysis examined the risk of incident asthma with a median follow-up to 3.0 (interquartile range, 2.1-3.0) years. Cox proportional hazards regression was used to estimate hazard ratios (HRs).
RESULTS
Among the 80 870 pairs (63.0% girls; mean [SD] age, 12.9 [4.8] years), those who initiated PPI use had a higher incidence rate of asthma (21.8 events per 1000 person-years) compared with noninitiators (14.0 events per 1000 person-years), with an HR of 1.57 (95% CI, 1.49-1.64). The risk of asthma was significantly increased across all age groups and was highest for infants and toddlers with an HR of 1.83 (95% CI, 1.65-2.03) in the group younger than 6 months and 1.91 (95% CI, 1.65-2.22) in the group 6 months to younger than 2 years (P < .001 for interaction). The HRs for individual PPIs were 1.64 (95% CI, 1.50-1.79) for esomeprazole, 1.49 (95% CI, 1.25-1.78) for lansoprazole, 1.43 (95% CI, 1.35-1.51) for omeprazole, and 2.33 (95% CI, 1.30-4.18) for pantoprazole. In analyses of the timing of asthma onset after PPI initiation, the HRs were 1.62 (95% CI, 1.42-1.85) for 0 to 90 days, 1.73 (95% CI, 1.52-1.98) for 91 to 180 days, and 1.53 (95% CI, 1.45-1.62) for 181 days to end of follow-up. The association was consistent through all sensitivity analyses, including high-dimensional propensity score matching (HR, 1.48; 95% CI, 1.41-1.55).
CONCLUSIONS AND RELEVANCE
In this cohort study, initiation of PPI use compared with nonuse was associated with an increased risk of asthma in children. Proton pump inhibitors should be prescribed to children only when clearly indicated, weighing the potential benefit against potential harm.
Topics: Adolescent; Asthma; Case-Control Studies; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Incidence; Infant; Infant, Newborn; Male; Propensity Score; Proportional Hazards Models; Proton Pump Inhibitors; Registries; Risk Factors; Sweden
PubMed: 33555324
DOI: 10.1001/jamapediatrics.2020.5710 -
JAMA Oct 2022In arthroscopic knee and shoulder surgery, there is growing evidence that opioid-sparing protocols may reduce postoperative opioid consumption while adequately... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of a Postoperative Multimodal Opioid-Sparing Protocol vs Standard Opioid Prescribing on Postoperative Opioid Consumption After Knee or Shoulder Arthroscopy: A Randomized Clinical Trial.
IMPORTANCE
In arthroscopic knee and shoulder surgery, there is growing evidence that opioid-sparing protocols may reduce postoperative opioid consumption while adequately addressing patients' pain. However, there are a lack of prospective, comparative trials evaluating their effectiveness.
OBJECTIVE
To evaluate the effect of a multimodal, opioid-sparing approach to postoperative pain management compared with the current standard of care in patients undergoing arthroscopic shoulder or knee surgery.
DESIGN, SETTING, AND PARTICIPANTS
This randomized clinical trial was performed at 3 clinical sites in Ontario, Canada, and enrolled 200 patients from March 2021 to March 2022 with final follow-up completed in April 2022. Adult patients undergoing outpatient arthroscopic shoulder or knee surgery were followed up for 6 weeks postoperatively.
INTERVENTIONS
The opioid-sparing group (100 participants randomized) received a prescription of naproxen, acetaminophen (paracetamol), and pantoprazole; a limited rescue prescription of hydromorphone; and a patient educational infographic. The control group (100 participants randomized) received the current standard of care determined by the treating surgeon, which consisted of an opioid analgesic.
MAIN OUTCOMES AND MEASURES
The primary outcome was postoperative oral morphine equivalent (OME) consumption at 6 weeks after surgery. There were 5 secondary outcomes, including pain, patient satisfaction, opioid refills, quantity of OMEs prescribed at the time of hospital discharge, and adverse events at 6 weeks all reported at 6 weeks after surgery.
RESULTS
Among the 200 patients who were randomized (mean age, 43 years; 73 women [38%]), 193 patients (97%) completed the trial; 98 of whom were randomized to receive standard care and 95 the opioid-sparing protocol. Patients in the opioid-sparing protocol consumed significantly fewer opioids (median, 0 mg; IQR, 0-8.0 mg) than patients in the control group (median, 40.0 mg; IQR, 7.5-105.0; z = -6.55; P < .001). Of the 5 prespecified secondary end points, 4 showed no significant difference. The mean amount of OMEs prescribed was 341.2 mg (95% CI, 310.2-372.2) in the standard care group and 40.4 mg (95% CI, 39.6-41.2) in the opioid-sparing group (mean difference, 300.8 mg; 95% CI, 269.4-332.3; P < .001). There was no significant difference in adverse events at 6 weeks (2 events [2.1%] in the standard care group vs 3 events [3.2%] in the opioid-sparing group), but more patients reported medication-related adverse effects in the standard care group (32% vs 19%, P = .048).
CONCLUSIONS AND RELEVANCE
Among patients who underwent arthroscopic knee or shoulder surgery, a multimodal opioid-sparing postoperative pain management protocol, compared with standard opioid prescribing, significantly reduced postoperative opioid consumption over 6 weeks.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04566250.
Topics: Acetaminophen; Adult; Analgesics, Non-Narcotic; Analgesics, Opioid; Anti-Ulcer Agents; Arthroscopy; Clinical Protocols; Drug Therapy, Combination; Female; Humans; Hydromorphone; Knee Joint; Male; Naproxen; Ontario; Pain, Postoperative; Pantoprazole; Patient Education as Topic; Postoperative Care; Shoulder Joint
PubMed: 36194219
DOI: 10.1001/jama.2022.16844 -
The Journal of the American Osteopathic... Dec 2019
Topics: Abdominal Pain; Anti-Bacterial Agents; Anti-Ulcer Agents; Emphysema; Foreign Bodies; Gastritis; Humans; Male; Melena; Middle Aged; Pantoprazole; Piperacillin, Tazobactam Drug Combination; Tomography, X-Ray Computed
PubMed: 31790130
DOI: 10.7556/jaoa.2019.140 -
Tuberculosis Research and Treatment 2020There is an urgent need for better and safer therapeutic interventions for tuberculosis (TB). We assessed the effects of FDA-approved ion transport modulators, namely,...
There is an urgent need for better and safer therapeutic interventions for tuberculosis (TB). We assessed the effects of FDA-approved ion transport modulators, namely, ambroxol HCl, amiloride HCl, diazoxide, digoxin, furosemide, hydrochlorothiazide (HCTZ), metformin, omeprazole, pantoprazole, phenytoin, verapamil, and drug X and Y on the growth of free and intracellular BCG. Free and intracellular BCG were cultured in the presence or absence of the test drugs for 3 to 9 days and then quantified. For both free and intracellular bacteria, cultures that were exposed to furosemide, phenytoin, or drug Y yielded lower bacteria counts compared to drug-free controls ( < 0.05). The same was observed with diazoxide, HCTZ, verapamil, and drug X, but only for intracellular BCG ( < 0.05). To assess the effects of the drugs on bactericidal activity of rifampicin, free and intracellular BCG were treated with rifampicin alone or in combination with each of the thirteen test drugs for 3 to 9 days. For extracellular bacteria, higher bacteria clearance rates were observed in cultures exposed to rifampicin in combination with amiloride HCl, diazoxide, digoxin, furosemide, HCTZ, metformin, pantoprazole, phenytoin, drug X, or drug Y than those exposed to rifampicin alone, indicating that rifampicin had a synergistic effect with these test drugs. Rifampicin was also synergistic with ambroxol HCl, diazoxide, digoxin, furosemide, HCTZ, omeprazole, pantoprazole, phenytoin, verapamil, and drug X against intracellular BCG. The antimycobacterial properties exhibited by the ion transport modulators in this study make them viable candidates as adjuncts to the current anti-TB regimens.
PubMed: 33294223
DOI: 10.1155/2020/3767915 -
Frontiers in Veterinary Science 2021Ruminant species are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for anti-ulcer therapies, such as the proton pump inhibitor...
Ruminant species are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for anti-ulcer therapies, such as the proton pump inhibitor pantoprazole, in goats. The primary study objective was to estimate the plasma pharmacokinetic parameters for pantoprazole in adult goats after intravenous administration. A secondary objective was to describe the pharmacokinetic parameters for the metabolite, pantoprazole sulfone, in goats. Pantoprazole was administered intravenously to six adult goats at a dose of 1 mg/kg. Plasma samples were collected over 36h and analyzed via reverse phase high performance liquid chromatography for determination of pantoprazole and pantoprazole sulfone concentrations. Pharmacokinetic parameters were determined by non-compartmental analysis. Plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 0.345 mL/kg/min, 0.7 h, and 0.9 L/kg, respectively following IV administration. The maximum concentration, elimination half-life and area under the curve of pantoprazole sulfone were estimated at 0.1 μg/mL, 0.8 h, and 0.2 hrμg/mL, respectively. The global extraction ratio was estimated 0.00795 ± 0.00138. All animals had normal physical examinations after conclusion of the study. The reported plasma clearance for pantoprazole is lower than reported for foals, calves, and alpacas. The elimination half-life appears to be < that reported for foals and calves. Future pharmacodynamic studies are necessary for determination of the efficacy of pantoprazole on acid suppression in goats.
PubMed: 34631865
DOI: 10.3389/fvets.2021.744813