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Can Probenecid Side Effects Help Inflammation?
Can Probenecid Side Effects Help Inflammation?

My current summary of probenecid side effects is outdated. So I'm renewing it based on the latest research. Which I have summarized below.

Probenecid Side Effects Research Topics

All the following studies refer to probenecid side effects. Particularly where gout patients display unwanted symptoms as a result of taking probenecid. In which case, those symptoms are often referred to as adverse events.

However, some side effects of probenecid are useful. Because they allow it to treat other diseases, besides gout. So I'll adopt the term innovative uses for these good side effects.

Probenecid History

My first study is an overview of probenecid history. With explanations of toxicity and side effects. Ending with a forward look at potential new uses.

Robbins, N., Koch, S.E., Tranter, M. and Rubinstein, J., 2012. The history and future of probenecid. Cardiovascular toxicology, 12(1), pp.1-9.

probenecid therapy has little to no hemopoietic, renal, or hepatic toxicity. The reported side effects of probenecid treatment included abdominal cramping, fever, rash, myalgia, shortness of breath, headaches, nausea, vomiting, and vasomotor collapse. The most common complaint after chronic therapy was gastrointestinal symptoms, but this was only reported in 78 of the 2,502 patients. The majority of these reported side effects were from patients on the maximum dose of 3 g/day; when this was reduced to 2 g/day, most of the symptoms subsided. Most of the adverse effects of probenecid are related to spontaneously provoked hypersensitivity reactions. […] probenecid has been administered millions of times to hundreds of thousands of people with very few adverse effects and almost no serious side effects. Although it has also been variously used and tested as treatment for depression, gastrointestinal diseases, eye pathology, and even as an inhibitor of steroid secretion in the urine

For innovative uses of probenecid, this study describes potential applications for heart and nervous system diseases

Due to its unique action and new findings implicating TRPV channels in physiology and in disease, probenecid may have a new future as a research tool, and perhaps as a clinical agent in the neurology and cardiology fields.

Tolerability of Probenecid

My second study investigates the capacity of probenecid to lower uric acid to safe levels. Together with an analysis of side effects that might prevent some gout patients using this treatment.

Pui, K., Gow, P.J. and Dalbeth, N., 2013. Efficacy and tolerability of probenecid as urate-lowering therapy in gout; clinical experience in high-prevalence population. The Journal of rheumatology, 40(6), pp.872-876.

Adverse events attributed to probenecid were observed in 10/57 patients (18%). One (1.8%) patient developed painful tongue, 2 (3.5%) developed headache, 1 (1.8%) had mouth ulcers, 2 (3.5%) had rashes, and 3 (5.3%) patients developed gastrointestinal side effects. One (1.8%) patient developed urolithiasis; this patient had a history of kidney stones and the calculus was not analyzed for its composition. Probenecid was discontinued in 7/57 patients (12%) because of adverse events.

This study does not consider innovative uses of probenecid.

Probenecid and Pain Control

My third study explains the low toxicity of probenecid. As it describes innovative uses in a wide range of neurological disorders. Including:

  • Parkinson’s Disease
  • Alzheimer’s Disease
  • Huntington’s Disease
  • Migraine
  • Ischemia
  • Epilepsy

Laura Colin-Gonzalez, A. and Santamaría, A., 2013. Probenecid: an emerging tool for neuroprotection. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders), 12(7), pp.1050-1065.

PROB [probenecid] has been used without major toxicity (Table 2). The reported side effects of PROB treatment (3 g/day) included abdominal cramping, fever, rash, myalgia, shortness of breath, headaches, nausea, vomiting, vasomotor collapse, urate kidney stones, and gastrointestinal symptoms, occurring in approximately. 3% of the general population. To our knowledge, there are two cases of immune hemolytic anemia associated with PROB, five cases that were related to nephrotic syndrome, a single case report of fatal hepatic necrosis, and only two cases of severe anaphylactoid reaction reported, with some actions reported when used as treatment for gonorrhea in pregnancy. Hypersensitivity reactions to PROB in the general population may occur as many as 2% to 4%. […] the many properties depicted by PROB this far, together with its lack of major side effects, serve to propose this drug not only as a valuable experimental tool to induce neuroprotection against toxic paradigms, but also as a promising agent for many clinical purposes

Among the many innovative uses explained in this study, control of pain and inflammation is of most importance to gout patients. Hence, my choice of an image from this study for my featured image in this article.

these pharmacological targets exert neuroprotective actions through the amelioration of excitatory events, a reduction of inflammatory processes and a modulation of nociception. These properties can help to explain why this drug, per se or in combination with other agents, exhibits beneficial effects in models of neurodegenerative disorders, migraine and ischemia.

Minimizing Probenecid Side Effects

My fourth study considers innovative uses for probenecid based on its gene-related actions. During which the authors describe how most probenecid side effects can be minimized by adjusting dosage and timing.

Ahmed, M.U., Bennett, D.J., Hsieh, T.C., Doonan, B.B., Ahmed, S. and Wu, J.M., 2016. Repositioning of drugs using open-access data portal DTome: A test case with probenecid. International Journal of Molecular Medicine, 37(1), pp.3-10.

Based on this evidence, the pattern, timing and dose in which probenecid is administered significantly influence the tolerability and likelihood of side effects occurring.

This study summarizes the diseases that are associated with probenecid as gout, viral infections, central nervous system infections, melanomas, breast cancer, and cellular cancer process.

Antiviral Probenecid Side Effects

Most recently, scientists have investigated the antiviral properties of probenecid as a potential treatment for COVID-19. Because they recognized that it had been successful in treating influenza in mice. Also, it has a history of being well-tolerated in gout patients.

Murray, J., Hogan, R.J., Martin, D.E., Blahunka, K., Sancilio, F.D., Balyan, R., Lovern, M., Still, R. and Tripp, R.A., 2021. Probenecid inhibits SARS-CoV-2 replication in vivo and in vitro. Scientific Reports, 11(1), pp.1-7.

Probenecid is a gout treatment, and is a favorable candidate for antiviral drug repurposing, as it is readily commercially available with favorable pharmacokinetics and has a benign clinical safety profile. […] The doses evaluated by the PK model were below the maximum allowable FDA-approved dose of 2 g/day and should have no substantial side effects. Together, these data strongly support the potential for probenecid to provide a robust antiviral response against SARS-CoV-2.
Can Probenecid Side Effects Help Inflammation?
Can Probenecid Side Effects Help Inflammation?

Your Probenecid Side Effects Research Story

Which aspects of probenecid side effects are you interested in? How do you think probenecid side effects might affect you and your gout?

Please tell me your probenecid side effects story in the Gout Forum.

This is my second probenecid research review…

  1. 2020 ACR Probenecid Guidelines
  2. This Probenecid Side Effects Research review
  3. Probenecid for Gout Comorbidities Research Studies

Leave Probenecid Side Effects Research to browse the Gout and Uric Acid Science Blog.

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