probenecid / Generic mfg. - LARVOL DELTA

A Clinical Study of MK-8527 in Healthy Participants (MK-8527-021) (clinicaltrials.gov) - P1 | N=44 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed

Hypoxia-mimicking Conditions Modulate ABC Transporter Expression And Function In Human Aortic Endothelial Cells (ERS 2026) - "P-gp and MRP4 inhibitors (verapamil, probenecid) increased rhodamine accumulation (181 ± 40% and 178 ± 15%, p < 0.0001), whereas BCRP inhibitor KO143 had no effect. Hypoxia upregulates P-gp and MRP4 and downregulates ABCA1 in aortic endothelial cells, promoting cholesterol accumulation. This may contribute to metabolic and cardiovascular dysfunction in OSA via altered drug transport, oxidative stress, lipid handling, and vascular integrity. Future studies will expose endothelial cells to plasma from OSA patients before and after CPAP therapy to examine ABC transporter regulation."

Cardiovascular • Inflammation • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder • ABCA1 • ABCG1

Disseminated adenovirus and rejection in a kidney transplant recipient: Walking the fine line between infection and rejection (TTS 2026) - "Primary renal pathology was anti glomerular basement membrane disease diagnosed in 2022, managed with therapeutic plasma exchange (TPE), corticosteroids and cyclophosphamide...Transplant induction regimen included tacrolimus, mycophenolate mofetil (MMF), basiliximab and corticosteroids...One month post kidney transplantation macroscopic haematuria developed and persisted despite therapy of Enterobacter cloacae and Streptococcus mitis bacteriuria with ciprofloxacin followed by ertapenem...Cidofovir was then commenced at 2.5mg/kg weekly for two weeks then fortnightly with probenecid and intravenous (IV) fluid therapy...This was treated with pulse IV methylprednisolone and MMF recommenced at 250mg twice daily. Follow up biopsy showed features of antibody mediated rejection which was managed with an increase in MMF and candesartan for a detected angiotensin receptor 1 antibody... We present a case of disseminated adenovirus infection post kidney transplantation. This case..."

Clinical • Antibody-mediated Rejection • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Pulmonary Embolism • Respiratory Diseases • Solid Organ Transplantation • Transplantation

Uremic toxin-induced pathological signaling in sinus node cells is attenuated by probenecid. (PubMed, Cardiorenal Med) - "These findings suggest that uremic toxin-driven stress signaling is associated with molecular remodeling signatures in sinus node cells under CKD-related conditions. Although the functional consequences of these molecular alterations were not assessed, probenecid attenuated uremic toxin-associated profibrotic, pro-apoptotic, and stress kinase signaling, suggesting that targeting molecular stress pathways may help strategy sinus node cell homeostasis in CKD."

IO biomarker • Journal • Chronic Kidney Disease • Fibrosis • Immunology • Nephrology • Renal Disease • BAX • BCL2 • TBX3

Drug-drug Interactions Studies of VC005 Tablets in Healthy Adult Subjects (clinicaltrials.gov) - P1 | N=84 | Not yet recruiting | Sponsor: Jiangsu vcare pharmaceutical technology co., LTD

New P1 trial

Synthesis of Pyridin-2(1H)-ones and Isoquinolin-1(2H)-ones Using Calcium Carbide as an Acetylene Source under Redox-Neutral Conditions. (PubMed, Org Lett) - "On the basis of this method, a number of pyridin-2(1H)-one and isoquinolin-1(2H)-one derivatives, including some hybrid products containing the essential skeleton of probenecid, ataluren, or adapalene, were obtained. In general, this protocol features simple and economical substrates, a safe and convenient acetylene source, the absence of an external oxidant, good compatibility with labile functional groups, excellent step and atom economy, and ready scalability. Moreover, some products possess strong anticancer activities."

Journal • Hepatitis C • Infectious Disease • Oncology

An Adaptive, Time-Informed, Phenotype-Guided Pharmacological Framework for Severe Traumatic Brain Injury : A Hypothesis-Driven Narrative Review. (PubMed, J Korean Neurosurg Soc) - "Glibenclamide/glyburide and hypertonic sodium lactate produced preliminary imaging or physiological signals without demonstrated functional benefit. Riluzole was neutral in an adult randomized trial, whereas a small study in chronic TBI found that minocycline reduced a neuroinflammatory imaging signal but increased plasma neurofilament light. Metformin and N-acetylcysteine plus probenecid provided exploratory pharmacokinetic, biomarker, or safety data. Amantadine provided phenotype-specific clinical proof of principle in traumatic disorders of consciousness. Cerebrolysin showed mixed human evidence, including a favorable day-90 multidimensional ensemble signal that requires independent replication. Deferoxamine and clemastine remain preclinical...Module activation should require optimized foundational care, a matching phenotype, measurable target activation or engagement, and acceptable systemic safety. This framework prioritizes phenotype-enriched, single-module..."

Journal • CNS Disorders • Vascular Neurology • Plasma NfL

Sustainable dual cobalt/photoredox catalysis for the selective synthesis of highly functionalized isoquinolones (ACS-Fall 2026) - "The methodology exhibits broad substrate scope, tolerating a variety of aromatic and heteroaromatic systems, including pharmacologically relevant motifs such as Probenecid and Xenalipin. Furthermore, a range of substituted allenes is compatible, providing access to highly functionalized products amenable to further derivatization. In conlusion, this work highlights the potential of combining cobalt catalysis and photoredox activation as a sustainable platform for the construction of complex molecular architectures."

Investigation of Tartaric Acid Enantiomer-Specific Nephrotoxicity and Citrate Synthase Inhibition in Madin-Darby Canine Kidney Cells In Vitro. (PubMed, J Vet Emerg Crit Care (San Antonio)) - "L-TTA is a species- and enantiomer-specific nephrotoxicant in dogs resulting from a lack of transporter-mediated efflux and subsequent citrate synthase inhibition. OAT-1 inhibition or OAT-4 transfection mitigates toxicity, supporting a transporter-driven mechanism for TTA accumulation."

Journal • Preclinical • Acute Kidney Injury • Nephrology • Renal Disease

AMPHORE: Enhancing Amoxicillin Pharmacokinetics and Pharmacodynamics Parameters With Probenecid in Bone and Joint Infections (clinicaltrials.gov) - P3 | N=57 | Not yet recruiting | Sponsor: Assistance Publique - Hpitaux de Paris

New P3 trial • Infectious Disease

Coproporphyrin I PBPK model in the open systems pharmacology suite enables precise prediction of OATP 1B- mediated drug interactions through calibrated In vivo inhibition constants. (PubMed, Front Pharmacol) - "It was integrated into a DDI network comprising the precipitants rifampicin, probenecid, and cyclosporine A, and the object drugs atorvastatin, pitavastatin, and rosuvastatin. It demonstrates that calibrating participant models using early clinical biomarker data enables reliable prospective prediction of OATP1B-mediated DDIs. This workflow supports model-informed drug development (MIDD) strategies, potentially reducing the need for dedicated clinical DDI studies."

Journal • Preclinical

Optimizing intravenous amoxicillin for outpatient parenteral antimicrobial therapy. (PubMed, JAC Antimicrob Resist) - "Amoxicillin's aqueous instability was not resolved by citrate buffering. However, for patients requiring IV therapy, probenecid-boosted intermittent and extended infusion regimens of amoxicillin appear to be promising alternatives that warrant further clinical investigation."

Journal

CYP2C19-Mediated Metabolic Activation and OAT3/P-gp-Associated Transport Contribute to Dioscorea bulbifera L.-Induced Hepatotoxicity. (PubMed, J Ethnopharmacol) - "These findings suggest that OAT3-sensitive cellular uptake, P-gp-mediated efflux, and CYP2C19-mediated bioactivation are important determinants of EEA hepatotoxicity, which is characterized by GSH depletion, cell-cycle perturbations, and apoptosis. This study provides a mechanistic explanation for DBL/EEA-induced hepatotoxicity and highlights that the interplay between metabolism and transport is a key determinant of its toxicity."

Journal • Hepatology • Liver Failure • CYP2C19

Tubular epithelial cells promote macrophage pyroptosis through PANX1-extracellular ATP-P2X7 signaling in aldosterone-dependent renal injury. (PubMed, Cell Death Dis) - "Urinary ATP levels and renal pannexin1 (PANX1, an ATP efflux channel) expression increased significantly in DOCA-salt mice, whereas the selective mineralocorticoid receptor (MR) antagonist finerenone treatment reduced urinary ATP levels, PANX1 expression, tubular injury, and macrophage-related inflammation. Inhibiting PANX1-eATP-P2X7 signaling with the PANX1 inhibitor probenecid, specifically knocking down tubular PANX1, or using the eATP ectonucleotidase apyrase or the P2X7 blocker AZ10606120 mitigated renal tubular damage and NLRP3-mediated pyroptosis in the renal cortex of DOCA-salt mice...PANX1-eATP-P2X7 signaling mediates TEC‒macrophage interactions to exacerbate Aldo-driven renal inflammation in hypertension. Mechanism through which Aldo/MR-induced PANX1-eATP-P2X7 signaling activation promotes macrophage pyroptosis in hypertensive renal injury."

Journal • Cardiovascular • Fibrosis • Hypertension • Immunology • Inflammation • Renal Disease • NLRP3

Probenecid enhances relaxation induced by cyclic adenosine monophosphate- and cyclic guanosine monophosphate-augmenting substances in rat prostate, bladder, and corpus cavernosum: a potential repurposing strategy. (PubMed, Eur J Pharmacol) - "In corpus cavernosum, probenecid induced relaxation per se and potentiated responses to acetylcholine, sodium nitroprusside, phosphodiesterase inhibitors, and β-agonists, with concurrent increases in both cAMP and cGMP. Selective tools targeting OAT1/3, P2X7 receptor and TRPV2 channels did not replicate these effects, whereas pannexin-1 inhibition potentiated acetylcholine-induced relaxation only in the corpus cavernosum. In conclusion, probenecid modulates smooth muscle relaxation across urogenital tissues and may represent a potential adjunct in the treatment of lower urinary tract symptoms and erectile dysfunction."

Journal • Preclinical • Benign Prostatic Hyperplasia • Erectile Dysfunction • TRPV2

Ultrasound-triggered platelet vehicles loading fluorescein for targeted sonodynamic therapy of glioblastoma. (PubMed, Drug Deliv) - "Platelets were loaded with fluorescein diacetate (FDA), a lipophilic prodrug that is converted intracellularly to active FL, combined with probenecid to inhibit MRP1-mediated efflux, generating the ultrasound-responsive [email protected] dual mechanism combines direct genotoxicity with impaired DNA repair capacity, underlying the potent anti-GBM efficacy. Our platelet-based FL delivery represents a practical, safe, translational therapy for overcoming BBB limitations by disabling HIF-1α-regulated DNA repair."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • Targeted Protein Degradation • HIF1A

Efficacy of amoxicillin compared to penicillin in acquired syphilis treatment (AIDS 2026) - "The 3.5 g/day amoxicillin regimen without probenecid appears to be effective in patients with and without HIV, justifying continuation of the study to assess non-inferiority to standard penicillin treatment."

Clinical • Human Immunodeficiency Virus • Immunology • Infectious Disease

Malignant syphilis with presumed multifocal osteomyelitis in a patient with human immunodeficiency virus: A case report. (PubMed, J Infect Chemother) - "This case underscores that malignant syphilis may be associated with clinically silent bone involvement detectable only through imaging studies. It also suggests that oral amoxicillin plus probenecid may represent an alternative treatment option when standard intramuscular penicillin therapy is not available."

Journal • Human Immunodeficiency Virus • Infectious Disease • Musculoskeletal Pain • Pain

Neisseria gonorrhoeae notifications, resistance and management in the Pilbara Region, Western Australia, July 2023 - June 2024. (PubMed, Commun Dis Intell (2018)) - "In October 2024, Pilbara treatment guidance for uncomplicated urogenital gonorrhoea shifted from routine ZAP pack (amoxicillin 3 g and probenecid 1 g and azithromycin 1 g oral as a single treatment) to ceftriaxone-based LAC pack (ceftriaxone 500 mg in 2 mL 1% lignocaine intramuscularly and azithromycin 1 g oral, as a single treatment) in response to rising penicillinase-producing N. gonorrhoeae (PPNG) and the threat of imported ciprofloxacin resistance. Reinforcing treatment consistent with the updated treatment guidelines of October 2024 for the Pilbara region will reduce the risk of ineffective treatment. Improving the rate of test of cure and test for reinfection (33%) would improve the likelihood of detecting treatment failure and detecting resistance."

Journal • Retrospective data • Infectious Disease

Progress report on new epilepsy treatments: A summary of the Eighteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVIII). I. Treatments in preclinical and early clinical development. (PubMed, Epilepsia) - "These include AUT00206, a positive allosteric modulator of Kv3.1 and Kv3.2 voltage-gated potassium channels in development for the treatment of rare epilepsy syndromes as well as neurodevelopmental and neuropsychiatric disorders; ION283, an antisense oligonucleotide designed to suppress the expression of glycogen synthase 1, under investigation for the treatment of Lafora disease; MSCA-7136, a selective allosteric RAS/mitogen-activated protein kinase-extracellular signal regulated kinase (MEK) inhibitor being developed for the treatment of focal seizures associated with mesial temporal lobe epilepsy and seizures associated with tuberous sclerosis complex; OV329, a selective inhibitor of γ-aminobutyric acid (GABA) aminotransferase, in development for the treatment of drug-resistant focal seizures; PTI5803 (probenecid), an uricosuric agent and a blocker of pannexin 1 channels, repurposed as a treatment for seizures associated with focal cortical dysplasia; simufilam, a..."

Journal • Preclinical • CNS Disorders • Developmental Disorders • Epilepsy • Mental Retardation • Psychiatry

Insights into amoxicillin pharmacokinetics using physiology-based pharmacokinetic modelling. (PubMed, Antimicrob Agents Chemother) - "The simulations also demonstrated high urinary amoxicillin exposures and evaluated the effects of inadequate active ingredient content, missed doses, and probenecid co-administration. This PBPK model gives the following insights into amoxicillin pharmacokinetics: i) the adequacy of amoxicillin for infections caused by S. pneumoniae and H. influenzae; ii) the impact of non-compliance and loss of active ingredients on antimicrobial coverage; iii) the effect of probenecid co-administration to improve coverage; and iv) the characterization of high urinary amoxicillin exposure with consequences for use in urinary tract infections."

Journal • PK/PD data • Infectious Disease • Influenza • Nephrology • Pneumococcal Infections • Pneumonia • Respiratory Diseases

Cisproplatin: A Redox-Activatable Cisplatin-Probenecid Pt(IV) Conjugate with Broad NCI-60 Potency that Decouples Antitumor Efficacy from Dose-Limiting Toxicity and Suppresses CIPN. (PubMed, J Med Chem) - "Pharmacokinetic analysis showed reduced renal platinum accumulation and prolonged circulation. Together, these data establish CPP as a redox-activatable dual-drug Pt(IV) platform that decouples robust anticancer potency from classical dose-limiting toxicity."

Journal • Oncology • Triple Negative Breast Cancer

Pharmacological modulation of TRPV2 enhances migration and induces Immunoglobulin E (IgE)-independent degranulation of mast cells. (PubMed, Cell Calcium) - "Using fluorometric Ca2+ influx assays and electrophysiological patch-clamp recordings, this study analyzes synergistic effects of the TRPV2 activators AV2-1, cannabidiol and probenecid...All observed effects were abolished by the TRPV2 inhibitor IV2-1 or genetic deletion of TRPV2 in transwell migration assays. These findings demonstrate that pharmacological activation of TRPV2 modulates mast cell effector functions and migration, supporting a role for TRPV2 as an immunomodulatory ion channel and a potential therapeutic target in immune system-related pathologies."

Journal • Immunology • CD63 • TRPV2

Flucloxacillin plasma and urinary concentrations with and without probenecid and urinary biomarker profiles in healthy volunteers. (PubMed, Br J Clin Pharmacol) - P4 | "Co-administration of probenecid significantly enhanced flucloxacillin exposure, without serious adverse effects. These findings warrant evaluation in a clinical trial of patients with MSSA infection."

Biomarker • Journal • Infectious Disease • KIM1

A Clinical Study of MK-8527 in Healthy Participants (MK-8527-021) (clinicaltrials.gov) - P1 | N=44 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open