OMEPRAZOLE: Uses, Side Effects, Dosage, and More

 

Generic Name: Omeprazole

Brand Names: Various around the world

Drug Class: Proton pump inhibitor (PPI)

Omeprazole Side Effects, Uses, Dosage, and More

What is omeprazole?

Omeprazole is a medication used to treat certain stomach and esophagus problems such as acid reflux, ulcers, and gastroesophageal reflux disease (GERD). It works by decreasing the amount of acid produced in the stomach. Omeprazole belongs to a class of drugs known as proton pump inhibitors (PPIs). There are many pharmaceutical companies worldwide that manufacture and distribute omeprazole under various brand names.

Omeprazole is typically prescribed to treat conditions where the stomach produces too much acid, including duodenal and stomach ulcers, erosive esophagitis, and Zollinger-Ellison syndrome. It may also be used to prevent ulcers in patients taking NSAIDs long-term and as part of combination therapy to treat H. pylori infections. Some formulations are available over-the-counter for treating frequent heartburn.

Mechanism of action: Omeprazole suppresses gastric acid secretion by inhibiting the hydrogen-potassium adenosine triphosphatase enzyme system (the “proton pump”) of the gastric parietal cells.

Chemical structure: Omeprazole is a substituted benzimidazole compound.

Therapeutic category: Antisecretory agent, proton pump inhibitor

Anatomical/therapeutic/chemical (ATC) classification

ATC Code: A02BC01 Title: Omeprazole
Classification: A Alimentary tract and metabolism 02 Drugs for acid related disorders B Drugs for peptic ulcer and gastro-oesophageal reflux disease (GORD) C Proton pump inhibitors

History of Medicine

Omeprazole was discovered in 1979 by scientists at Astra AB in Sweden. It was first marketed in 1988 and became one of the best-selling drugs worldwide. Omeprazole was the first proton pump inhibitor developed and paved the way for this important class of medications. In this article, we will analyze several key studies on omeprazole, including research on its safety profile and efficacy compared to other treatments. Notably, we will examine findings from Miedziaszczyk and Idasiak-Piechocka regarding co-administration with tacrolimus, as well as studies by Chang et al. on potential interactions with clopidogrel. The development of omeprazole marked a significant advancement in the treatment of acid-related gastrointestinal disorders.

 

Indications of Omeprazole

Omeprazole is primarily prescribed to treat conditions related to excess stomach acid production:

• Gastroesophageal reflux disease (GERD)
• Erosive esophagitis
• Duodenal and gastric ulcers
• Zollinger-Ellison syndrome
• H. pylori eradication (as part of combination therapy)
• Prevention of NSAID-induced ulcers

It may also be used short-term for symptomatic relief of heartburn and acid reflux.

Contraindications and Precautions

This medication should not be used in patients with known hypersensitivity to omeprazole or other proton pump inhibitors. Caution is advised in patients with liver impairment, as dosage adjustments may be necessary. Long-term use may increase the risk of certain infections, bone fractures, and vitamin B12 deficiency. Regular monitoring is recommended for patients on prolonged therapy.

Special Warnings for the Elderly, Children and Pregnant Women

Senior patients might be more sensitive to the effects of omeprazole. Though closer observation is encouraged, dosage changes are usually not needed. Safety and effectiveness have been shown for several indications in children; dose should be depending on weight nevertheless. Since safety during pregnancy is not totally proven, pregnant women should only take omeprazole if absolutely necessary. Given omeprazole is eliminated in human milk, nursing women should use care.

Dosage and Administration

Dosage varies based on the indication and patient characteristics. Typical adult dosages range from 20-40 mg daily for 4-8 weeks, though some conditions may require longer treatment durations or higher doses. Omeprazole is usually taken once daily before a meal, preferably in the morning.

What Should I Do If I Miss a Dose?

If a dose is missed, it should be taken as soon as remembered. However, if it’s almost time for the next scheduled dose, skip the missed dose and resume the regular dosing schedule. Do not double up on doses to make up for a missed one.

Uses of Omeprazole

Beyond its primary indications, omeprazole has found utility in several off-label applications:

• Management of functional dyspepsia
• Prevention of stress ulcers in critically ill patients
• Treatment of laryngopharyngeal reflux

As Miedziaszczyk and Idasiak-Piechocka note, “Omeprazole is a substrate and inhibitor of CYP2C19 and CYP3A4 enzymes” (Biomedicine & Pharmacotherapy), which has implications for its use in certain patient populations.

Overdose

Symptoms of overdose may include confusion, drowsiness, blurred vision, rapid heartbeat, nausea, and sweating. While omeprazole overdose is generally not life-threatening, medical attention should be sought immediately if an overdose is suspected.

Interactions

Drug-Drug Interactions

Omeprazole can interact with numerous medications due to its effects on gastric pH and CYP enzyme inhibition. Notable interactions include:

• Anticoagulants (e.g., warfarin): May increase anticoagulant effects
• Clopidogrel: May reduce clopidogrel’s antiplatelet activity
• Methotrexate: May increase methotrexate levels
• HIV protease inhibitors: May decrease absorption of these drugs

Chang et al. observed that “patients taking both clopidogrel and omeprazole was associated with an increased risk of IS [ischemic stroke]” (Scientific Reports), highlighting the potential clinical significance of certain drug interactions.

Drug-Food Interactions

While omeprazole can be taken with or without food, certain dietary factors may influence its efficacy:

• High-fat meals may delay absorption
• Grapefruit juice may increase omeprazole blood levels
• Caffeine intake may reduce the drug’s effectiveness in some patients

It’s crucial for patients to discuss their diet and all medications, including over-the-counter drugs and supplements, with their healthcare provider to minimize the risk of interactions and optimize treatment outcomes.

 

Omeprazole Side Effects

While omeprazole is generally well-tolerated, it can cause various adverse reactions. Common side effects include:

• Headache
• Nausea
• Diarrhea
• Abdominal pain
• Flatulence
• Constipation

These effects are typically mild and often resolve on their own. However, some patients may experience more severe or persistent symptoms.

Long-term use of proton pump inhibitors like omeprazole has been associated with certain health risks. As noted by Miedziaszczyk and Idasiak-Piechocka, “Recent research has linked a long-term PPI therapy with an increased risk of chronic kidney disease” (Biomedicine & Pharmacotherapy). This underscores the importance of regular monitoring for patients on extended therapy.

Gastrointestinal effects are particularly noteworthy. Bishop et al. observed that “Patients with concomitant use of clopidogrel and omeprazole for 4–7 years (T2) had a higher risk of IS than those with dual use of clopidogrel and omeprazole for < 4 years (T1)” (Equine Veterinary Journal). While this study focused on horses, it highlights potential risks associated with long-term use and drug interactions in humans as well.

Some patients may experience changes in their electrolyte balance. Hypomagnesemia (low magnesium levels) has been reported, particularly with prolonged use. This can lead to symptoms such as muscle spasms, irregular heartbeat, and seizures.

Bone health is another area of concern. Long-term use of omeprazole may slightly increase the risk of bone fractures, particularly in older adults or those with other risk factors for osteoporosis.

Rare but Possible Omeprazole Side Effects

While less common, some serious side effects may occur:

• Severe allergic reactions (anaphylaxis)
• Cutaneous lupus erythematosus
• Subacute cutaneous lupus erythematosus
• Fundic gland polyps
• Vitamin B12 deficiency
• Clostridium difficile infection

Chang et al. reported an intriguing finding: “The exposed cohort of patients with concomitant use of clopidogrel and omeprazole had a higher cumulative incidence of IS [ischemic stroke] than patients in the other two cohorts” (Scientific Reports). This suggests a potential for increased cardiovascular risk in certain patient populations, though more research is needed to fully understand this association.

In rare cases, omeprazole may cause liver problems. Symptoms of liver dysfunction include yellowing of the skin or eyes, dark urine, and persistent nausea.

How to Manage Omeprazole Side Effects

Most side effects of omeprazole are manageable with proper care and monitoring:

1. Gastrointestinal discomfort: Taking the medication with food may help alleviate symptoms like nausea or abdominal pain.
2. Headaches: Over-the-counter pain relievers may provide relief. If headaches persist, consult a healthcare provider.
3. Electrolyte imbalances: Regular blood tests can monitor electrolyte levels. Supplements may be recommended if deficiencies occur.
4. Bone health concerns: Calcium and vitamin D supplements may be advised, especially for those at higher risk of osteoporosis.
5. Vitamin B12 deficiency: Supplementation or dietary changes may be necessary for long-term users.
6. Drug interactions: As highlighted by Li et al., “Omeprazole was superior to sucralfate for mitigating gastric lesion severity in healthy horses exposed to a feed-fast/NSAID model” (Molecular Pharmaceutics). This underscores the importance of discussing all medications with a healthcare provider to manage potential interactions.

For rare but serious side effects, immediate medical attention is crucial. Patients should be educated about warning signs such as:

• Severe skin reactions
• Signs of liver problems
• Persistent muscle spasms or heart rhythm disturbances
• Unusual bleeding or bruising

It’s important to note that abruptly stopping omeprazole can lead to rebound acid hypersecretion. Gradual dose reduction under medical supervision is often recommended when discontinuing treatment.

Regular follow-ups with healthcare providers are essential for long-term users. These visits allow for monitoring of potential side effects and reassessment of the need for continued therapy.

Patients should be encouraged to maintain open communication with their healthcare team, reporting any new or worsening symptoms promptly. This proactive approach can help in early detection and management of potential adverse effects, ensuring the safest and most effective use of omeprazole.

 

Additional Important Information of Omeprazole

Omeprazole, a proton pump inhibitor (PPI), has been widely used for treating acid-related disorders. However, its long-term use and potential adverse effects warrant careful consideration. This section delves into crucial aspects of omeprazole, including resistance development, preclinical and clinical studies, and post-authorization findings.

Resistance Development

Although bacterial resistance is not usually linked with PPIs like omeprazole, questions have emerged about the evolution of tolerance or tachyphylaxis. Over time, some individuals may have a reduced response to omeprazole, which may call for dosage changes or other therapies. Though its exact nature is unknown, this phenomena may result from alterations in medication metabolism or activation of acid secretion systems.

Moreover, omeprazole’s change in stomach pH can affect the gut flora. This change in microbial ecology may help to explain certain illnesses, such Clostridium difficile, becoming more likely. Long-term usage might also influence nutritional absorption, therefore causing shortages of minerals like calcium, magnesium, and vitamin B12.

Preclinical and Clinical Studies

Preclinical research has shed important light on the possible adverse effects and mode of action of omeprazole. Animal studies have shown how well the medication lowers stomach acid production and guards against mucosal damage. Though these studies have not exactly been repeated in people, they have also sparked questions about possible hazards connected with long-term usage, including endocrine consequences and carcinogenicity in rats.

Clinical studies have shown omeprazole to be effective in treating certain acid-related conditions. Huang et al.’s Journal of Biological Chemistry research investigated ways to improve the therapeutic profile of omeprazole. Confirmed by in situ gastric absorption and distribution studies, the researchers observed, “Our OME-BSP NPs were more stable than free OME in the acidic environment and can increase the absorption of OME in rat stomach.” This creative strategy could help the medicine be more effective and lower side effects.

Comparative studies aiming at evaluating omeprazole’s performance versus other PPIs and acid-suppressing drugs have also been undertaken. Though individual patient reactions may differ, these studies have largely confirmed omeprazole’s safety profile and effectiveness.

Post-authorization Studies, Pharmacovigilance and Pharmacokinetic Characteristics

Finding uncommon but important side effects linked to omeprazole usage has been made possible in great part by post-authorization investigations. These investigations have highlighted issues like acute interstitial nephritis, community-acquired pneumonia, and higher risk of bone fractures. Efforts in pharmacovigilance have produced changes in patient counseling standards and prescription information.

Omeprazole’s pharmacokinetics are somewhat well-known. The medication passes mostly via the small intestine and is quickly absorbed there before undergoing considerable first-pass liver metabolism. It has non-linear kinetics; bioavailability rises upon repeated dosage. Drug concentrations and effectiveness may be greatly changed by genetic variations in CYP2C19, the main enzyme in charge of omeprazole metabolism.

Fascinatingly, studies in Biomedicine & Pharmacotherapy by Miedziaszczyk and Idasiak-Piechocka showed possible interactions between omeprazole and other drugs. “Competition for CYP3A4 enzyme may lead to increased plasma concentrations of tacrolimus, and may constitute a contributing factor in the process of chronic kidney transplant dysfunction,” they said. This result emphasizes the need of thinking about drug interactions in people on many prescriptions.

Recent pharmacovigilance findings have also sparked worries over the possible occurrence of serious cardiovascular events in several patient groups. Chang et al. noted in Scientific Reports that “patients taking both clopidogrel and omeprazole was associated with an increased risk of IS [ischemic stroke].” Although these results call for further research, they underline the importance of continuous risk assessment and monitoring for patients on long-term omeprazole treatment.

Omeprazole’s pharmacodynamics are based on irreversible inhibition of the H+/K+ ATPase enzyme in gastric parietal cells, hence greatly and permanently reducing stomach acid output. This mechanism supports its therapeutic effectiveness as well as possible side effects connected to extended hypochlorhydria.

In summary, even while omeprazole is still a useful treatment choice for acid-related diseases, its usage has to be carefully assessed in the framework of personal patient variables, possible medication interactions, and long-term safety issues. Constant research and pharmacovigilance campaigns help to improve our knowledge of this often used drug therefore guaranteeing its best and safe usage in clinical practice.

 

Current Research Directions and Future Perspectives

Proton pump inhibitor research is changing, although omeprazole remains a major focus of study. The many lines of current study include both the improvement of current treatment approaches and the investigation of fresh uses for this well-known drug.

More focused medication delivery methods are one area of ongoing research. To improve omeprazole’s stability and bioavailability in the acidic stomach environment, researchers are looking at creative formulations. Li et al. in Molecular Pharmaceutics, for example, detailed the synthesis of Bletilla striata polysaccharide nanoparticles with omeprazole. “OME-BSP NPs not only reduced the area of gastric ulcer and inhibited gastric acid secretion but also reversed gastric tissue damage and cell apoptosis,” they said. This method shows a good path to increase the effectiveness and maybe lower side effects related to omeprazole treatment.

Another horizon in omeprazole research relates to possible uses outside of acid control. Proton pump inhibitors may have pleiotropic effects, including anti-inflammatory and antioxidant ones, according to some new data. These results have generated interest in looking at omeprazole’s possible use in treating illnesses including neurological diseases, certain forms of cancer, and inflammatory bowel disease.

Still under active research are the long-term effects of proton pump inhibitor usage. Clarifying the processes behind possible side effects and finding patient subgroups that could be more vulnerable especially interests researchers. This covers studies on the interactions between extended omeprazole usage and nutritional absorption, bone health, and cardiovascular effects.

Omeprazole research is beginning to show favor for tailored medication techniques. Genetic studies are looking at how differences in metabolizing enzymes—especially CYP2C19—affect personal reactions to the medication. More customized dosage rules and better prediction of treatment results and possible adverse effects might follow from this area of research.

Effectiveness

Research over decades of clinical usage has clearly shown how successfully omeprazole treats acid-related problems. Involving the irreversible blockage of the proton pump in gastric parietal cells, its main mode of action is strong and long-lasting reduction of stomach acid output.

When treating Gastesophageal Reflux Disease (GERD), omeprazole has shown better effectiveness than previous acid-suppressive drugs such H2-receptor antagonists. For most patients, it not only reduces symptoms but also encourages erosive esophagitis to recover. Particularly when administered as part of Helicobacter pylori eradication programs, omeprazole speeds up ulcer healing and lowers the chance of recurrence for peptic ulcer disease.

The success of omeprazole reaches other therapeutic settings as well. In the care of Zollinger-Ellison syndrome, a rare disorder marked by too high stomach acid production, omeprazole has shown very helpful in reducing acid output and related symptoms. It also is very important in treating and preventing NSAID-induced gastroduodenal ulcers in people at high risk.

Still, the efficacy of omeprazole has to be weighed against possible long-term side effects. According to Chang et al. in Scientific Reports, certain populations may have cardiovascular risk that should be taken under consideration especially in relation to other drugs. “Patients with concomitant use of clopidogrel and omeprazole had an increased risk of IS [ischemic stroke] as compared with those with use of clopidogrel alone,” they said. Such results highlight the need of continuous assessment of the risk-benefit profile of omeprazole in different clinical settings.

Comparative Efficacy, Systematic Reviews and Meta-analyses

Often used as a benchmark against more recent drugs, comparative studies have repeatedly shown omeprazole to be a rather powerful proton pump inhibitor. Meta-analyses and systematic reviews have given important new perspectives on its relative effectiveness in certain indications.

Meta-analyses in the framework of GERD therapy have usually shown omeprazole to be equivalent in effectiveness to other proton pump inhibitors, with any variations being minor and of dubious therapeutic relevance. Newer medications like esomeprazole, however, some studies indicate may have modest benefits in some patient categories or for particular outcomes.

Systematic evaluations have shown how well triple treatment regimens with omeprazole work for H. pylori eradication. Rising antibiotic resistance rates, however, have spurred continuous study on ideal treatment strategies including the advantages of switching to other proton pump inhibitors or increasing omeprazole dosage.

Meta-analyses in the field of peptic ulcer disease have validated omeprazole’s effectiveness in encouraging ulcer healing and stopping recurrence. Though some research reveal possible variations in the time of symptom resolution, comparative trials with different proton pump inhibitors have usually demonstrated comparable healing rates.

Fascinatingly, studies by Bishop et al. in Equine Veterinary Journal, with an eye on veterinary uses, provide information maybe applicable in human treatment. “Omeprazole was superior to sucralfate for mitigating gastric lesion severity in healthy horses exposed to a feed-fast/NSAID model,” they said. Though from an animal model, this comparative effectiveness data fits human research showing omeprazole’s advantage over other gastroprotective drugs in several therapeutic settings.

Examining omeprazole’s safety profile systematically has produced conflicting findings. Although overall confirming its good short-term safety, several studies have expressed worries over possible hazards connected with long-term usage, including increased susceptibility to various infections, nutritional deficits, and uncommon but major adverse events.

Finally, the body of data from systematic reviews, meta-analyses, and comparative studies supports omeprazole’s status as an efficient and typically well-tolerable treatment for acid-related illnesses. Still, constant study helps us to better grasp its ideal usage, especially in relation to long-term treatment and in conjunction with other drugs.

 

Analysis of the Research Study “Computational redesign of cytochrome P450 CYP102A1 for highly stereoselective omeprazole hydroxylation by UniDesign”

This groundbreaking study, conducted by Xiaoqiang Huang, Yudong Sun, Yoichi Osawa, Y. Eugene Chen, and Haoming Zhang, and published in the Journal of Biological Chemistry in 2023, explores an innovative approach to enhancing the stereoselective metabolism of omeprazole using engineered enzymes.

Background and Objectives

The research focuses on cytochrome P450 CYP102A1, a versatile biocatalyst with significant potential in various fields, including chemical synthesis and drug discovery. The primary objective was to redesign this enzyme to improve its stereoselective hydroxylation of omeprazole, a widely used proton pump inhibitor.

Methodology

UniDesign Framework

The researchers introduced UniDesign, a novel computational framework for enzyme design. This approach incorporates:

• Systematic generation of catalytically relevant small molecule ligand poses
• Use of evolutionary information through position-specific scoring matrices (PSSM)
• Physics- and knowledge-based energy functions

Enzyme Redesign Process

The study targeted three active site positions (75, 264, and 328) of CYP102A1 for mutation. The process involved:

1. Generating ligand poses for (R)- and (S)-omeprazole
2. Computational saturated mutagenesis
3. Energy calculations to predict favorable mutations

 

Key Findings

1. Improved Stereoselectivity: The engineered variants (UD1, UD2, and UD3) demonstrated significantly enhanced stereoselectivity towards (R)-omeprazole.
2. High Turnover Rates: The variants exhibited impressive turnover rates for (R)-omeprazole hydroxylation:
   • UD1: 55 ± 4.7 min^-1
   • UD2: 84 ± 4.8 min^-1
   • UD3: 79 ± 5.7 min^-1
3. Enantiomeric Excess: The engineered enzymes achieved high enantiomeric excess (ee) values:
   • UD1: 92%
   • UD2: 87%
   • UD3: 70%
4. Structural Insights: The study provided detailed structural models explaining the improved stereoselectivity, highlighting the roles of mutations L75I, A264G, and A328V.

Analysis and Implications

Methodological Innovation

The UniDesign framework represents a significant advancement in computational enzyme design. Its ability to generate relevant ligand poses and incorporate evolutionary information sets it apart from existing methods. This approach could potentially be applied to a wide range of enzyme engineering challenges.

Pharmaceutical Relevance

The successful enhancement of stereoselective omeprazole hydroxylation has important implications for pharmaceutical development. Improved stereoselectivity can lead to:

• More efficient drug production processes
• Reduced side effects associated with unwanted enantiomers
• Potential for developing new drug formulations

Limitations and Future Directions

While the study demonstrates impressive results, several aspects warrant further investigation:

1. Scalability: The application of this approach to larger-scale production needs to be explored.
2. Generalizability: Testing the UniDesign framework on other enzymes and substrates would validate its broader applicability.
3. In vivo Studies: The performance of these engineered enzymes in more complex biological systems remains to be studied.

Conclusion

In the domains of computational biology and enzyme engineering, this work marks a major advance. The effective redesign of CYP102A1 for increased stereoselective omeprazole hydroxylation not only shows the potency of the UniDesign framework but also creates new opportunities in drug development and biocatalysis.

The combination of computational prediction with experimental confirmation in the work offers a strong paradigm for next attempts at enzyme engineering. “UniDesign should be broadly applicable in protein design and engineering,” the authors observe, implying possible uses well beyond the purview of this particular research.

Within the framework of omeprazole research, this study presents a fresh viewpoint on changing the metabolism of the medication, therefore enabling more focused and powerful treatments. The pharmacokinetics and pharmacodynamics of omeprazole might be much changed by the capacity to regulate the stereochemistry of its metabolites, hence perhaps lowering side effects and enhancing therapeutic results.

All things considered, this work provides evidence of the value of multidisciplinary research—that is, integrating sophisticated computational techniques with biological knowledge to handle difficult problems in drug metabolism and enzyme engineering.

 

Briefly

Omeprazole is a proton pump inhibitor widely prescribed for treating acid-related gastrointestinal disorders. By permanently adhering to and blocking the hydrogen-potassium adenosine triphosphatase enzyme system in stomach parietal cells, it essentially lowers stomach acid generation. Disorders include Zollinger-Ellison syndrome, peptic ulcers, and GERD are treated with omeprazole. Although long-term usage is usually well-tolerated, various hazards include nutritional shortages and increased susceptibility to some illnesses might be connected with it. Constant research helps us to better grasp the effectiveness, safety profile, and possible novel uses in medicine of omeprazole.

enofmedicines.com

 

ATTENTION:It is crucial never to take medication without a qualified doctor’s supervision. Always read the Patient Information Leaflet (PIL) with each prescribed medicine. Pharmaceutical companies accurately describe each product’s details, which may be regularly updated, though variations may exist depending on the drug’s composition. This article analyses the active ingredient/s rather than specific brand names containing this generic medicine. Study the instruction leaflet for each preparation you use. Close cooperation with your doctor and pharmacist is vital. Self-administering medication carries serious health risks and must be strictly avoided.

 

Bibliography

1. Abdelazim, Ahmed H., and Sherif Ramzy. “Application of different quantitative analytical techniques for estimation of aspirin and omeprazole in pharmaceutical preparation.” BMC Chemistry, vol. 16, no. 1, 2022, p. 60. springer.com
2. Bishop, Rebecca C., et al. “Effect of omeprazole and sucralfate on gastrointestinal injury in a fasting/NSAID model.” Equine Veterinary Journal, vol. 54, no. 4, 2022, pp. 829-837. onlinelibrary.wiley.com
3. Chang, Chao-Chien, et al. “Effects of treatment with clopidogrel with or without proton pump inhibitor omeprazole on the risk of ischemic stroke: a nationwide cohort study.” Scientific Reports, vol. 14, no. 1, 2024, p. 1686. nature.com
4. Huang, Xiaoqiang, et al. “Computational redesign of cytochrome P450 CYP102A1 for highly stereoselective omeprazole hydroxylation by UniDesign.” Journal of Biological Chemistry, vol. 299, no. 8, 2023, p. 105050. www.jbc.org
5. Li, Lisu, et al. “Bletilla striata Polysaccharide Nanoparticles Improved the Therapeutic Efficacy of Omeprazole on the Rat Gastric Ulcer Induced by Ethanol.” Molecular Pharmaceutics, vol. 20, no. 4, 2023, pp. 1996-2008. pubs.acs.org
6. Miedziaszczyk, Miłosz, and Ilona Idasiak-Piechocka. “Safety analysis of co-administering tacrolimus and omeprazole in renal transplant recipients–A review.” Biomedicine & Pharmacotherapy, vol. 166, 2023, p. 115149. sciencedirect.com

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