probenecid / Generic mfg. - LARVOL DELTA

Biodistribution and Pathophysiology Study of 11C-para-aminobenzoic Acid (clinicaltrials.gov) - P=N/A | N=13 | Completed | Sponsor: Johns Hopkins University | Recruiting ➔ Completed | N=30 ➔ 13 | Trial completion date: Nov 2027 ➔ Nov 2025 | Trial primary completion date: Nov 2026 ➔ Nov 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Infectious Disease • Inflammation

Lysophosphatidylcholine sensitizes TRPV2 by indirect mechanisms. (PubMed, Pflugers Arch) - "However, 3 µM LPC induced a reversible potentiation of membrane currents induced by 2-APB, cannabidiol (CBD), probenecid (PBC) and weak acids, but not to heat...A disruption of the actin cytoskeleton with cytochalasin D, but also the depletion of cholesterol or sphingomyelin from the cell membrane diminished the potentiating effects of LPC on TRPV2. In conclusion, we present novel data describing that the PLA2 downstream signaling lipid LPC amplifies TRPV2-mediated responses via indirect mechanisms that seem to involve a destabilization of lipid rafts and the actin cytoskeleton."

Journal • Cardiovascular • Oncology • Pain • TRPV2

Pharmacokinetics of Sulopenem Etzadroxil Plus Probenecid in Adolescents (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Iterum Therapeutics, International Limited | Initiation date: Sep 2025 ➔ Jan 2026 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial initiation date • Infectious Disease

Effect of ibuprofen on the pharmacokinetics of intravenous flucloxacillin in healthy adults. (PubMed, Int J Antimicrob Agents) - "Orally administered ibuprofen had no measurable effect on plasma flucloxacillin PK in healthy adults. Given the lack of drug-drug interaction, there is no benefit to prescribe ibuprofen alongside flucloxacillin to increase flucloxacillin exposure."

Journal • PK/PD data • Infectious Disease • Pain

A Study to Learn About How the Study Medicines Called Itraconazole and Probenecid Change How the Body Processes PF-07220060 (clinicaltrials.gov) - P1 | N=28 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open

Probenecid Treatment Inhibits Replication of the Edmonston Measles Virus Strain in Vero Cells. (PubMed, Viruses) - "MeV treatments may include vitamin A, ribavirin, the MeV vaccine, or human immunoglobulin for pregnant patients exposed to MeV but lacking immunity. This study indicates that pre-treatment with probenecid (prophylaxis) can inhibit the replication of the Edmonston MeV strain in VeroE6 cells (1.12 μM) and Vero-SLAM cells (1.03 μM), while treatment (1 h post-infection, hpi) inhibits replication in VeroE6 cells (1.32 μM) and Vero-SLAM cells (8.66 μM). These results suggest that probenecid is an effective, host-directed antiviral drug against MeV replication in vitro."

Journal • Infectious Disease • Measles • Mumps • Rubella

Colon-Specific Delivery of Probenecid Enhances Therapeutic Activity of the Uricosuric Agent Against Rat Colitis. (PubMed, Pharmaceutics) - "Moreover, PBN-GA therapeutically surpassed sulfasalazine, a currently used anti-IBD drug, in rat colitis. These results suggest that amide conjugation with GA can be used to design a colon-targeting prodrug for PBN. Colon-targeted PBN may not only enhance therapeutic effectiveness but also improve the safety of PBN repositioned for the treatment of IBD and may be a pharmacological alternative for current small-molecule anti-IBD drugs with low efficacy or serious adverse effects with long-term use."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Gout • Immunology • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Rheumatology

Vormatrigine Exhibits a Favorable Drug-Drug Interaction Profile Supporting Broad Combination Use with Antiseizure Medications (AES 2025) - "Key enzymes assessed included CYP1A2, 2C19, 3A4, and UGT isoforms, along with major efflux and uptake transporters.Clinically, the Phase 1 PRAX-628-102 study enrolled healthy adults and examined the pharmacokinetics (PK) of single 10 mg doses of vormatrigine alone and in combination with fluvoxamine (CYP1A2/2C19 inhibitor), itraconazole (CYP3A4 inhibitor) and probenecid (non-selective UGT inhibitor). Vormatrigine exhibits a highly favorable DDI profile, supported by both preclinical mechanistic studies and human PK data. With no clinically meaningful interactions observed with inhibitors or inducers of major CYP and UGT pathways—except a moderate effect via CYP1A2—vormatrigine is well-suited for use in multi-drug epilepsy regimens, including a broad array of ASMs without the need for dose adjustments. These findings reinforce vormatrigine's potential as a best-in-class sodium channel modulator and support its continued clinical development in the ENERGY program for..."

CNS Disorders • Epilepsy • ABCB1 • CYP1A2

Beyond Parathyroid: A Mystery of Refractory Hypercalcemia Requiring Hemodialysis (KIDNEY WEEK 2025) - "Case Description A 61-year-old woman with CKD3, nephrolithiasis, gout (on probenecid-colchicine), and birdshot retinopathy (on methotrexate, prednisone), immunocompromise from chronic steroid and methotrexate use, presented with syncope, confusion and constipation...Her hypercalcemia did not respond to intravenous fluids, but improved transiently with calcitonin, zoledronic acid and antibiotics for PJP. She eventually responded to denosumab combined with transient hemodialysis and stabilized with steroids (Figure 1)...Our patient was discharged on prednisone and dapsone, and off methotrexate and probenecid. She had subsequent improvement in hypercalcemia and chest X-ray findings, suggesting resolution due to PJP treatment and medication optimization."

Constipation • Endocrine Disorders • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Gout • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammatory Arthritis • Metabolic Disorders • Nephrology • Pneumonia • Renal Calculi • Renal Disease • Respiratory Diseases • Retinal Disorders • Rheumatology • Sarcoidosis • Solid Organ Transplantation • Tuberculosis

A Case of Refractory Calcinosis in Juvenile Dermatomyositis (KIDNEY WEEK 2025) - "Her skin, joint, and muscle disease went into remission in her 20s after treatment with methotrexate, mycophenolate mofetil, azathioprine, TNF inhibitors, rituximab, and glucocorticoids...Treatment with sodium thiosulfate, colchicine, simvastatin, and calcium-channel blockers (CCB) was attempted but refractory...Treatment is based on case series, with colchicine, sodium thiosulfate, probenecid, CCBs, bisphosphonates, and TNF inhibitors showing variable results...This case highlights the need for further study of refractory calcinosis and current therapeutic limitations. Multiple bulky cutaneous and muscular calcifications throughout the chest wall."

Clinical • Dermatomyositis • Immunology • Infectious Disease • Metabolic Disorders • Musculoskeletal Pain • Myositis • Nephrology • Renal Disease • Rheumatology

Role of the Mineralocorticoid Receptor in Hemodialysis Vascular Access Dysfunction (KIDNEY WEEK 2025) - "Methods Human umbilical vein endothelial cells (HUVECs) and venous SMCs were cultured and treated with the MR agonist aldosterone, as well as the MRAs spironolactone and finerenone...The effects of pro-inflammatory stimuli (TNF-α) and the uremic toxin indoxyl sulfate on MR activation were also evaluated, along with the potential suppressive roles of MRAs and antioxidants (N-acetyl cysteine, probenecid)...Conclusion MR activation in venous ECs and SMCs promotes SMC proliferation, oxidative stress, and inflammation, contributing to vascular access stenosis. The non-steroidal MRA finerenone effectively attenuates these processes and may serve as a promising therapeutic strategy to prevent vascular access failure in dialysis patients."

Inflammation • TNFA

Two Therapeutic Approaches for Vancomycin-Associated AKI: Urinary Acidification or Inhibition of Organic Anion Transporters with Probenecid (KIDNEY WEEK 2025) - "Conclusion This study demonstrates that urinary acidification and inhibition of OAT via probenecid significantly reduce vancomycin-associated AKI. These findings suggest promising preventive strategies to mitigate nephrotoxicity in clinical practice."

Renal Disease

The Treatment of Cognitive Deficits in HIV-1 gp120 Tg Mice: Reduction of Inflammatory Infiltration in the Hippocampus By Kynurenine Acid (ASH 2024) - "Because peripheral KYNA is unable to cross the blood-brain barrier, we intraperitoneally injected gp120 tg mice with the KYNA precursor kynurenine (KYN) and probenecid (PROB), which inhibits KYNA loss.Methods : All mice were divided into 2 groups : gp120 tg + PBS, gp120 tg + KYN and PROB...After injection of KYN and PROB, the number of neurons in the gp120 tg mice hippocampal area remained at normal levels, with a mild reduction in cell volume and slight inflammatory cell infiltration.Conclusion : KYN/KYNA ameliorated cognitive deficits and neuropathologic deficits in gp120 tg mice via blood-brain barrier. These findings provide new evidence for the treatment of HAND with KYNA."

Preclinical • Anesthesia • CNS Disorders • Cognitive Disorders • Developmental Disorders • Human Immunodeficiency Virus • Infectious Disease • Inflammation

The Re-Prosper HF Study (clinicaltrials.gov) - P2/3 | N=99 | Active, not recruiting | Sponsor: VA Office of Research and Development | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jun 2025 ➔ Dec 2025

Enrollment closed • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure

Sulopenem etzadroxil/probenecid (Orlynvah) for uncomplicated UTIs. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Infectious Disease • Nephrology

Redefining uUTI therapy: Orlynvah as a promising oral alternative (sulopenem etzadroxil and probenecid). (PubMed, Ann Med Surg (Lond)) - "The efficacy of Orlynvah was established through two large multicenter trials, which demonstrated superior outcomes compared to amoxicillin-clavulanate and improved efficacy over ciprofloxacin in cases involving resistant pathogens. The drug was generally well-tolerated, with few serious adverse events reported. Orlynvah offers a promising oral alternative in the era of rising antimicrobial resistance and represents a significant advancement in the management of uUTIs."

Journal • Infectious Disease • Nephrology

Patient and Caregiver Perspectives on the Burden of Disease in Uncontrolled Gout: A Cross-Sectional Survey Study (ACR Convergence 2025) - "Patients were currently using the following ULT treatments: allopurinol (49%), pegloticase (26%), febuxostat (20%), and probenecid (4%). This is the first study to present data on caregiver burden associated with UG, highlighting significant challenges and reduced HRQOL for caregivers and patients with UG. Both reported HRQOL below the general US population with the largest impact in physical health-related domains, likely due to clinical manifestations of UG for patients, and for caregivers, the physical demands of caring for a patient. Employed individuals also experienced notable work impairment demonstrating the multifaceted impacts of UG."

Clinical • HEOR • Gout • Inflammatory Arthritis • Rheumatology

A Gain-of-function 5'UTR Variant in ANKH Causes Familial CPPD with Elevated Extracellular Ppi and Citrate (ACR Convergence 2025) - "Treatment of fibroblasts with probenecid (5 mM), an ANKH inhibitor, abolished the increased citrate levels observed in the proband's fibroblast culture media... We describe a novel 5'UTR variant in the ANKH gene that generates an ectopic start codon. Functional studies showed increased extracellular levels of PPi and citrate and overexpression of ENPP1 without alterations in ANKH mRNA or protein levels, supporting a gain-of-function mechanism"

Immunology • Metabolic Disorders • Rheumatology • ENPP1 • IL6 • MMP1 • TNFRSF11B

Simultaneous inhibition of pannexin-1 by probenecid and caspases by Z-VAD-fmk attenuates apoptosis and necroptosis in a rat model of cerebral ischemia-reperfusion. (PubMed, Neurol Res) - "This dual-targeting strategy effectively limits cell death and inflammation. Importantly, these findings may help explain the limited success of prior anti-apoptotic monotherapies in stroke and emphasize the necessity of targeting both apoptosis and necroptosis to achieve meaningful neuroprotection."

Journal • Preclinical • Cardiovascular • Inflammation • Reperfusion Injury • CASP3 • CASP8 • RIPK1 • TNFA

18β-Glycyrrhetinic Acid Regulates Endoplasmic Reticulum Stress and Autophagy Dysregulation in the MPTP/p-Induced Model of Parkinson Disease. (PubMed, Mol Neurobiol) - "This study is the first to explore the potential neuroprotective effects of 18βGA in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p)-induced mouse model of PD, focusing on the role of ER stress and autophagy and examining the potential underlying mechanisms...These findings suggest that 18βGA confers neuroprotection by suppressing ER stress (via PERK and IRE1α pathways) and modulating autophagy through the BCL-2/Beclin-1 axis. Thus, 18βGA holds promise as a therapeutic candidate for Parkinson disease."

IO biomarker • Journal • B Cell Lymphoma • CNS Disorders • Lymphoma • Movement Disorders • Oncology • Parkinson's Disease • BCL2 • BECN1 • ERN1 • HSPA5 • MAP1LC3B • MAPK8

Use of cimetidine to enhance systemic acyclovir concentrations in patients with ineffective suppressive therapy for recurring herpes simplex virus infections: A novel purpose for an old drug. (PubMed, Br J Clin Pharmacol) - "We report a series of patients nonresponsive to suppressive valacyclovir therapy, explained by subtherapeutic acyclovir plasma levels. After a dose increase, or in some patients only after concomitant prescription of cimetidine, adequate levels were reached associated with significant clinical improvement."

Journal • Herpes Simplex • Infectious Disease

Inhibition of Pannexin1 alleviates the damage of pilocarpine-induced status epilepticus through diminishing inflammatory PANoptosis-like neuron death. (PubMed, Int Immunopharmacol) - "Utilizing the Panx1 inhibitor probenecid improved the epileptic EEG and cognitive dysfunction in SE mice by mitigating neuron loss. These results suggest the presence of PANoptosis-like neuron death in epileptic injury. Our findings also suggest that Panx1 may be involved in PANoptosis, identifying Panx1 as a crucial regulator of the neuroinflammatory response in the context of epilepsy."

Journal • CNS Disorders • Cognitive Disorders • Epilepsy • Inflammation

Probenecid relieves LPS-induced neuroinflammation by modulating the NLRP1 inflammasome pathway in BV2 cells. (PubMed, Sci Rep) - "However, the NLRP1 inflammasome activator (muramyl dipeptide, MDP) reversed the effects of Prob. In conclusion, Prob could alleviate LPS-induced inflammation by modulating the NLRP1 inflammasome pathway."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • Movement Disorders • Oncology • Parkinson's Disease • IL1B • MRC1 • NLRP1 • TNFA

Rational Design of Probenecid-Functionalized Silicon Phthalocyanine J-Aggregated Nanoshuttles for Lipid Droplet-Targeted Drug-Resistant Theranostics. (PubMed, Adv Healthc Mater) - "These properties collectively contributed to potent PDT efficacy against both cancer cells and drug-resistant strains, underscoring its potential as a theranostic platform capable of overcoming resistance mechanisms. This work establishes a blueprint for developing transporter-modulated theranostic nanomaterials offering organelle-level diagnostic precision."

Journal • Oncology

MFN2-a multifaceted guardian against Parkinson's pathophysiology: mitochondria, ferroptosis, inflammation and oxidative stress. (PubMed, Front Aging Neurosci) - "In vivo, C57BL/6 J male mice were administered MPTP and probenecid by intraperitoneal injection to establish PD models...Mitochondrial morphological observation showed that MFN2 overexpression alleviated mitochondrial abnormalities. MFN2 may play a protective role in PD by regulating mitochondrial function, ferroptosis, inflammation and oxidative stress-related factors, providing a new theoretical basis and potential therapeutic targets for the treatment of PD."

Journal • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • AIFM2 • DHODH • GPX4 • MFN1 • MFN2