-
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 -
Nature Communications Dec 2023Target trial emulation is the process of mimicking target randomized trials using real-world data, where effective confounding control for unbiased treatment effect...
Target trial emulation is the process of mimicking target randomized trials using real-world data, where effective confounding control for unbiased treatment effect estimation remains a main challenge. Although various approaches have been proposed for this challenge, a systematic evaluation is still lacking. Here we emulated trials for thousands of medications from two large-scale real-world data warehouses, covering over 10 years of clinical records for over 170 million patients, aiming to identify new indications of approved drugs for Alzheimer's disease. We assessed different propensity score models under the inverse probability of treatment weighting framework and suggested a model selection strategy for improved baseline covariate balancing. We also found that the deep learning-based propensity score model did not necessarily outperform logistic regression-based methods in covariate balancing. Finally, we highlighted five top-ranked drugs (pantoprazole, gabapentin, atorvastatin, fluticasone, and omeprazole) originally intended for other indications with potential benefits for Alzheimer's patients.
Topics: Humans; Alzheimer Disease; Drug Repositioning; Propensity Score; Atorvastatin
PubMed: 38081829
DOI: 10.1038/s41467-023-43929-1 -
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 -
European Journal of Case Reports in... 2023Pantoprazole is one of the most widely used proton pump inhibitors, but anaphylaxis occurs rarely during its use. The purpose of reporting these two cases is to show...
INTRODUCTION
Pantoprazole is one of the most widely used proton pump inhibitors, but anaphylaxis occurs rarely during its use. The purpose of reporting these two cases is to show that pantoprazole is not a drug without problems; it can also cause anaphylactic reactions.
CASES DESCRIPTION
A 42-year-old woman presented to the emergency department due to dyspeptic complaints. Immediately at the end of the infusion of pantoprazole, there started to be numbness of the tongue, itching all over the body, and difficulty in breathing. Half an hour after taking a pantoprazole 40 mg capsule, a 58-year-old woman started to experience redness of the face, thickening of the tongue, itching, bloating, and dizziness. Arterial pressure was 80/60 mmHg, pulse 150/minute, while saturation had dropped to 88%. In both cases, fluids, adrenaline, antihistamines, methylprednisolone, and calcium were immediately started. After the improvement of their general conditions, both patients were discharged home.
DISCUSSION
The first case relates to anaphylaxis after the intravenous administration of pantoprazole, and the second case relates to the appearance of anaphylaxis after its oral administration.
CONCLUSION
Health workers need to be informed about the possibility of anaphylaxis in patients taking both oral and parenteral pantoprazole.
LEARNING POINTS
PPIs are generally safe, with a low percentage of side effects of 1-3%.Although hypersensitive reactions to PPIs are rare, cases of anaphylactoid reactions have also been reported in the literature.Anaphylaxis caused by taking pantoprazole should be considered in the differential diagnosis of anaphylaxis in both oral and parenteral administration of the drug.Doctors and pharmacists should be very careful when prescribing pantoprazole and other PPIs, especially to the elderly.
PubMed: 37680781
DOI: 10.12890/2023_004017 -
Danish Medical Journal Jun 2020Polypharmacy is associated with an increased risk of adverse health outcomes. This study aims to describe the prevalence of polypharmacy and medication use among older...
INTRODUCTION
Polypharmacy is associated with an increased risk of adverse health outcomes. This study aims to describe the prevalence of polypharmacy and medication use among older Danish citizens.
METHODS
From national registers, we extracted medicine use in relation to age group and residential region for the entire Danish population for the first half of 2016. The most frequently redeemed medicines among older citizens (≥ 75 years) in 2016 were grouped into clinically meaningful medication classes.
RESULTS
The prevalence of polypharmacy (> 5 different medicines) was 51% among citizens ≥ 75 years compared with 12% for the entire Danish population. The prevalence of polypharmacy increased with age and was 7% among citizens aged 40-49 years compared with 66% among citizens aged ≥ 90 years. There were only minor regional differences in the prevalence of polypharmacy. The most commonly redeemed medicine classes and individual medicines for older citizens were: 1) pain medication: paracetamol (50%) and tramadol (14%); 2) cardiovascular medicines: acetylsalicylic acid (26%), simvastatin (25%), metoprolol (22%), amlodipine (21%), furosemide (20%), bendroflumethiazide (17%), and losartan (14%); and 3) gastrointestinal medicines: pantoprazole (15%).
CONCLUSIONS
Polypharmacy is prevalent in Denmark with no relevant regional differences. The prevalence of polypharmacy increased with age, and more than half of the population aged ≥ 75 years redeemed prescriptions for > 5 different medicines. The most redeemed medicines among older citizens were against pain and cardiovascular disease.
FUNDING
none.
TRIAL REGISTRATION
not relevant.
Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Child; Child, Preschool; Cross-Sectional Studies; Denmark; Drug Prescriptions; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Polypharmacy; Prevalence; Young Adult
PubMed: 32741431
DOI: No ID Found -
Frontiers in Veterinary Science 2022Development of abomasal ulceration is a large concern, especially within calves; however, there is a paucity of research into the use of gastro protectants in ruminant...
INTRODUCTION
Development of abomasal ulceration is a large concern, especially within calves; however, there is a paucity of research into the use of gastro protectants in ruminant species. Proton pump inhibitors, such as pantoprazole, are widely used in humans and companion animals. Their efficacy in ruminant species is undetermined. The objectives of this study were to 1) estimate the plasma pharmacokinetic parameters for pantoprazole in neonatal calves after three days of intravenous (IV) or subcutaneous (SC) administration, and 2) measure the effect pantoprazole had on abomasal pH over the treatment period.
METHODS
Pantoprazole was administered to 6 Holstein-Angus cross bull calves at a dose of 1 mg/kg (IV) or 2 mg/kg (SC), once a day (every 24 h) for three days. Plasma samples were collected over a 72 h period and analyzed HPLC-UV for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Abomasal (n= 8) samples were collected abomasal cannulas over a 12 h period, per calf per day. Abomasal pH was determined a bench top pH analyzer.
RESULTS
Following Day 1 of IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 199.9 mL/kg/h, 1.44 h, and 0.51 L/kg, respectively. On Day 3 of IV administration, the reported values were 192.9 mL/kg/h, 2.52 h, and 1.80 L/kg mL, respectively. Elimination half-life and volume of distribution (V/F) of pantoprazole following SC administration were estimated at 1.81 h and 0.55 L/kg, respectively, on Day 1; and 2.99 h and 2.82 L/kg, respectively, on Day 3.
DISCUSSION
The reported values for IV administration were similar to those previously reported in calves. SC administration appears to be well absorbed and tolerated. The sulfone metabolite was detectable for 36 h after the last administration for both routes. Abomasal pH was significantly higher than the pre-pantoprazole pH 4, 6, and 8 h after administration in both the IV and SC groups. Further studies of pantoprazole as a treatment/preventative for abomasal ulcers are warranted.
PubMed: 36794231
DOI: 10.3389/fvets.2022.1101461 -
Pharmacogenomics and Personalized... 2023Proton pump inhibitors (PPIs) are commonly used medications to treat acid-related conditions, including gastro-esophageal reflux disease (GERD). Gastroenterology... (Review)
Review
Proton pump inhibitors (PPIs) are commonly used medications to treat acid-related conditions, including gastro-esophageal reflux disease (GERD). Gastroenterology guidelines mention the importance of CYP2C19 in PPI metabolism and the influence of genetic variations on variable responses to PPIs, but do not currently recommend the genotyping of prior to prescribing PPIs. There are strong data to support the influence of genetic variations on the pharmacokinetics of PPIs and clinical outcomes. Existing pharmacogenetic guideline recommendations for dose increases focus on and erosive esophagitis indications, but PPIs are also the main therapy for treating GERD. Recent data suggest GERD patients being treated with a PPI may also benefit from genotype-guided dosing. We summarize the literature supporting this contention and highlight future directions for improved management of patients with GERD through precision medicine approaches.
PubMed: 37383676
DOI: 10.2147/PGPM.S371994 -
Saudi Pharmaceutical Journal : SPJ :... Mar 2022have a major role in nosocomial infections leading to high morbidity and mortality. Increased resistance to various antifungals, especially azoles is a significant...
have a major role in nosocomial infections leading to high morbidity and mortality. Increased resistance to various antifungals, especially azoles is a significant problem. One of the main mechanisms for azole resistance is the up-regulation of efflux pump genes including and . In the current study, clinical isolates were identified to the species level and the antifungal susceptibility (AFS) of different was determined by disk diffusion method. Furthermore, the main mechanisms of azole resistance were investigated. Finally, haloperidol and pantoprazole were tested for their potential synergistic effect against fluconazole-resistant isolates. One hundred and twenty-two clinical isolates were used in this study. 70 isolates were (57.4%), the non-albicans include: (20.5%), (6.6%), (5.7%), (4.9%) and (4.9%). The AFS testing showed that resistance to fluconazole and voriconazole were 13.1% (n = 16) and 9.8% (n = 12), respectively. Among the 16 resistant isolates, eight isolates (50%) were strong biofilm producers, seven (43.8 %) formed intermediate biofilm and one had no biofilm. All resistant strains overexpressed efflux pumps. Using RT-PCR, the efflux genes , and were over-expressed in azole resistant isolates. Haloperidol-fluconazole and pantoprazole-fluconazole combinations reduced the MIC of fluconazole in resistant isolates. The current study showed an increase in azole resistance of . The majority of resistant isolates form biofilm, and overexpress efflux pumps. Pantoprazole and Haloperidol showed a noteworthy effect as efflux pump inhibitors which oppose the fluconazole resistance in different .
PubMed: 35498219
DOI: 10.1016/j.jsps.2022.01.011 -
Cureus May 2021Due to its minimal side-effect profile, immunotherapy has become a popular choice for the treatment of advanced melanoma as compared to conventional chemotherapy. The...
Due to its minimal side-effect profile, immunotherapy has become a popular choice for the treatment of advanced melanoma as compared to conventional chemotherapy. The most common side effects associated with immunotherapy include gastrointestinal, pulmonary, and dermatologic manifestations. However, there have been very few documented occurrences of nephrotoxic side effects. We present a case of a 73-year-old male with a past medical history of chronic kidney disease (CKD) stage 3A, metastatic uveal melanoma, and gastroesophageal reflux disease on pantoprazole who arrived at the intensive care unit with altered mental status and creatinine of 27 gm/dl (baseline creatinine of 3 gm/dl about one year prior), after receiving his first dose of ipilimumab and nivolumab approximately 21 days prior. Kidney biopsy demonstrated acute tubulointerstitial nephritis (ATIN). This case highlights the importance of recognizing acute tubulointerstitial nephritis as a side effect of immunotherapy for prompt diagnosis and early treatment.
PubMed: 34164249
DOI: 10.7759/cureus.15358 -
Medicinski Glasnik : Official... Aug 2021Aim To present a unique case of a 22-year-old male patient with symptomatic epilepsy manifestation on a background of neurocysticercosis (NCC). Methods An Indian student...
Aim To present a unique case of a 22-year-old male patient with symptomatic epilepsy manifestation on a background of neurocysticercosis (NCC). Methods An Indian student in Kharkiv, who lived in rural parts in India, presented with sudden episodes of seizure followed by severe headaches. Laboratory analyses and neurological status (MRI) were performed. Results Neurological status of the patient revealed nystagmus and difficulty in performing co-ordination tests. General analysis of blood showed raised eosinophil count to 8%. The MRI showed a few small conglomerating peripherally enhancing thick-walled infective granulomas in left frontal lobe with extensive surrounding oedema in the left fronto-parietal lobe. The patient was treated with albendazol, levipil, methylprednisolone and pantoprazole. Clinical symptoms and subsequent MRI showed improvement. Conclusion Neurocysticercosis is often misdiagnosed in the early stages, which leads to adverse outcomes. Although seizures are the most common clinical manifestation, it is a symptom that is not found in majority of the patients. The NCC of adult onset accompanying epileptic seizures is not well studied and a link between the helminthic invasion, epilepsy and psychiatric conditions needs to be established. This disease is potentially eradicable with wellplanned eradication programs targeting all stages of life cycle.
Topics: Adult; Animals; Brain; Epilepsy; Humans; Male; Neurocysticercosis; Seizures; Taenia solium; Young Adult
PubMed: 34190505
DOI: 10.17392/1368-21