Delving into the Latest Updates on Capreomycin Sulfate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Capreomycin, Capreomycin disulfate, Capreomycin sulfate (JAN/USP)

+ [7]

Target

30S subunit x 50S subunit

Action

inhibitors

Mechanism

30S subunit inhibitors(30S ribosomal subunit inhibitors), 50S subunit inhibitors(50S ribosomal subunit inhibitors)

Therapeutic Areas

Infectious DiseasesRespiratory Diseases

Active Indication

Pulmonary Tuberculosis

Inactive Indication-

Originator Organization

Epic Pharma LLC

Eli Lilly & Co.

Active Organization

Henan Taifeng Biotechnology Co., Ltd.

Liaoning Beiqi Pharmaceutical Co., Ltd.

Inactive Organization

Matinas BioPharma Holdings, Inc.

Epic Pharma LLCEli Lilly Canada, Inc.

Drug Highest PhaseApproved

First Approval Date

United States (02 Jun 1971),

Pulmonary Tuberculosis

Regulation-

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To determine the demographic, behavioral, clinical, and geographic risk factors associated with the occurrence of multidrug-resistant pulmonary tuberculosis (MDRTB). To evaluate the clinical and microbiological responses and overall survival of MDRTB patients who are treated with levofloxacin-containing multiple-drug regimens chosen from a hierarchical list. Per 9/28/94 amendment, to assess whether persistent or recurrent positive sputum cultures of patients who show failure or relapse are due to the same strain or reinfection with a new strain.
Among TB patients, there has been an increase in progressive disease due to the emergence of antimycobacterial drug-resistant strains of Mycobacterium tuberculosis. Failure to identify patients at high risk for MDRTB increases the hazard for both treatment failure and development of resistance to additional therapeutic agents. Efforts to improve survival in patients with MDRTB will depend on improved methods of assessing the risk of acquisition of MDRTB and identifying drug susceptibility patterns in a timely fashion.

Start Date-

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

NCT02496572

/ Unknown statusNot ApplicableIIT

Effectiveness of a Simplified Short Regimen for Multidrug Resistant Tuberculosis Treatment in Karakalpakstan, Uzbekistan

Multidrug resistant tuberculosis (MDR TB) is a growing problem and few people have access to adequate diagnosis and treatment. The current recommended treatment regimen for MDR TB has a minimum of 20 months duration with high toxicity. Scale up of MDR TB treatment is associated with high default rates, and experience in the Medecins Sans Frontieres (MSF) programme in Uzbekistan shows that the current standard treatment greatly limits the ability to scale up to meet the high rates of MDR TB in the region.
Evidence from Bangladesh in 2010 showed that a 9-month short-course regimen could achieve a relapse-free cure rate of 88%. Several countries in West Africa started implementing similar regimens with similar outcomes. Evidence of effectiveness of this shortened regimen among regions with high second line drug use and resistance is still limited.
The investigators propose an observational study under programmatic conditions to evaluate the effectiveness of a shortened course MDR TB regimen in the high MDR/extensively drug resistant (XDR) TB prevalence and high second-line drug resistance setting of Karakalpakstan, Uzbekistan.

Start Date01 Sep 2013

Sponsor / Collaborator

Medecins Sans Frontières (UK)

[+1]

NCT00042289

/ CompletedNot ApplicableIIT

Pharmacokinetic Properties of Antiretroviral and Related Drugs During Pregnancy and Postpartum

IMPAACT P1026s is a Phase IV prospective clinical study to evaluate the pharmacokinetics (PKs) of antiretroviral (ARV) and tuberculosis (TB) medications in pregnant women and their infants. (Pharmacokinetics are the various interactions between a drug and the body.) This study also evaluated the PKs of certain ARVs in postpartum women before and after starting hormonal contraceptives. The PKs of these drugs were evaluated by measuring the amount of medicine present in blood and/or vaginal secretions.

Start Date09 Jun 2003

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

[+1]

100 Clinical Results associated with Capreomycin Sulfate

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100 Translational Medicine associated with Capreomycin Sulfate

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100 Patents (Medical) associated with Capreomycin Sulfate

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689

Literatures (Medical) associated with Capreomycin Sulfate

01 Mar 2025·The Lancet Infectious Diseases

Evaluating culture-free targeted next-generation sequencing for diagnosing drug-resistant tuberculosis: a multicentre clinical study of two end-to-end commercial workflows

Article

Author: Colman, Rebecca E ; Suresh, Anita ; De la Rossa, Andres ; Omar, Shaheed V ; Kambli, Priti ; Georghiou, Sophia B ; Hoogland, Christine ; Uplekar, Swapna ; Laurent, Sacha ; Maghradze, Nino ; Rodrigues, Camilla ; Rodwell, Timothy C ; Tukvadze, Nestani ; Seifert, Marva ; Joseph, Lavania

BACKGROUNDDrug-resistant tuberculosis remains a major obstacle in ending the global tuberculosis epidemic. Deployment of molecular tools for comprehensive drug resistance profiling is imperative for successful detection and characterisation of tuberculosis drug resistance. We aimed to assess the diagnostic accuracy of a new class of molecular diagnostics for drug-resistant tuberculosis.METHODSWe conducted a prospective, cross-sectional, multicentre clinical evaluation of the performance of two targeted next-generation sequencing (tNGS) assays for drug-resistant tuberculosis at reference laboratories in three countries (Georgia, India, and South Africa) to assess diagnostic accuracy and index test failure rates. Eligible participants were aged 18 years or older, with molecularly confirmed pulmonary tuberculosis, and at risk for rifampicin-resistant tuberculosis. Sensitivity and specificity for both tNGS index tests (GenoScreen Deeplex Myc-TB and Oxford Nanopore Technologies [ONT] Tuberculosis Drug Resistance Test) were calculated for rifampicin, isoniazid, fluoroquinolones (moxifloxacin, levofloxacin), second line-injectables (amikacin, kanamycin, capreomycin), pyrazinamide, bedaquiline, linezolid, clofazimine, ethambutol, and streptomycin against a composite reference standard of phenotypic drug susceptibility testing and whole-genome sequencing.FINDINGSBetween April 1, 2021, and June 30, 2022, 832 individuals were invited to participate in the study, of whom 720 were included in the final analysis (212, 376, and 132 participants in Georgia, India, and South Africa, respectively). Of 720 clinical sediment samples evaluated, 658 (91%) and 684 (95%) produced complete or partial results on the GenoScreen and ONT tNGS workflows, respectively, with 593 (96%) and 603 (98%) of 616 smear-positive samples producing tNGS sequence data. Both workflows had sensitivities and specificities of more than 95% for rifampicin and isoniazid, and high accuracy for fluoroquinolones (sensitivity approximately ≥94%) and second line-injectables (sensitivity 80%) compared with the composite reference standard. Importantly, these assays also detected mutations associated with resistance to critical new and repurposed drugs (bedaquiline, linezolid) not currently detectable by any other WHO-recommended rapid diagnostics on the market. We note that the current format of assays have low sensitivity (≤50%) for linezolid and more work on mutations associated with drug resistance is needed.INTERPRETATIONThis multicentre evaluation demonstrates that culture-free tNGS can provide accurate sequencing results for detection and characterisation of drug resistance from Mycobacterium tuberculosis clinical sediment samples for timely, comprehensive profiling of drug-resistant tuberculosis.FUNDINGUnitaid.

01 Jan 2025·Drugs

Long-Term Self-Administered Outpatient Parenteral Antimicrobial Therapy in the Treatment of Tuberculosis

Article

Author: Brehm, T T ; Kalsdorf, B ; Lange, C ; Schaub, D ; Stoycheva, K ; Köhler, N ; Maier, C ; Böttcher, L ; Rauch, A ; Reimann, M ; Schmiedel, S ; Friesen, I ; Zielinski, N

OBJECTIVESTo investigate the safety profiles and clinical outcomes in a continuous cohort of tuberculosis (TB) patients from a clinical referral centre in Germany receiving self-administered outpatient parenteral antimicrobial therapy (sOPAT).METHODSWe conducted a retrospective observational cohort study of patients receiving sOPAT after discharge from the Research Center Borstel in Germany between January 2015 and December 2020. Data were extracted from medical records.RESULTSIn the observation period, 150 patients received parenteral antibiotics at the Research Center Borstel. Of these, 89 received sOPAT via a port catheter and were further analysed. The majority were male (n = 59, 66.3%), with a median age of 33.6 years (interquartile range-IQR 26.2-42.8). Most patients had multidrug-resistant (MDR)-TB (n = 56, 62.9%) or pre-extensively drug resistant (pre-XDR)-TB (n = 21; 23.6%). Fifty-eight (65.2%) patients received one and 24 patients (27.0%) received two parenteral drugs, most commonly capreomycin (n = 53, 59.6%) and meropenem (n = 44, 49.4%). The median duration of sOPAT was 7.4 months (IQR 5.2-17.2). In total, 71,128 intravenous drug administrations were recorded. One patient died of TB while another patient was lost to follow-up. Sixty-two (69.7%) patients completed the sOPAT regimen, the most common reason for premature discontinuation was adverse drug events (n = 12, 13.5%). There were eight (9.0%) port-related complications requiring port explantation (bloodstream infections: n = 6, local infection: n = 1, port thrombosis: n = 1).CONCLUSIONSIn selected patients requiring long-term intravenous anti-TB therapy, sOPAT is a feasible treatment option with a low risk of complications when adequate infrastructure and training are in place.

26 Nov 2024·Chemistry – A European Journal

What is the Origin of the Regioselective C₃‐Hydroxylation of L‐Arg by the Nonheme Iron Enzyme Capreomycin C?

Article

Author: Warwicker, Jim ; Wong, Henrik P. H. ; Hay, Sam ; Cao, Yuanxin ; de Visser, Sam P.

AbstractThe nonheme iron dioxygenase capreomycin C (CmnC) hydroxylates a free L‐arginine amino acid regio‐ and stereospecifically at the C3‐position as part of the capreomycin antibiotics biosynthesis. Little is known on its structure, catalytic cycle and substrate specificity and, therefore, a comprehensive computational study was performed. A large QM cluster model of CmnC was created of 297 atoms and the mechanisms for C3−H, C4−H and C5−H hydroxylation and C3−C4 desaturation were investigated. All low‐energy pathways correspond to radical reaction mechanisms with an initial hydrogen atom abstraction followed by OH rebound to form alcohol product complexes. The work is compared to alternative L‐Arg hydroxylating nonheme iron dioxygenases and the differences in active site polarity are compared. We show that a tight hydrogen bonding network in the substrate binding pocket positions the substrate in an ideal orientation for C3−H activation, whereby the polar groups in the substrate binding pocket induce an electric field effect that guides the selectivity.

100 Deals associated with Capreomycin Sulfate

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External Link

KEGG	Wiki	ATC	Drug Bank
D00135	Capreomycin Sulfate	J04AB30	DB00314

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Pulmonary Tuberculosis	China	Liaoning Beiqi Pharmaceutical Co., Ltd.	01 Jan 1996
Pulmonary Tuberculosis	China	Henan Taifeng Biotechnology Co., Ltd.	01 Jan 1996

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Infectious Diseases	Phase 2	United States	Matinas BioPharma Holdings, Inc.	31 Dec 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASN2018	Not Applicable	Chronic Kidney Diseases	-	Capreomycin	zmuxkmodlw(lvhziehpvs) = This case demonstrates a rapid, severe alteration of the GFR in a diabetic, normotensive patient with no evident proteinuria. The biopsy did not reveal kidney impairment from the DM. The literature reports few cases on nephrotoxicity from CPM. This study emphasizes the importance of strict controlling the GFR in patients on CPM, especially the elderly and those with comorbidities. jxbuucsmdw (vdfflllzfr )	-	23 Oct 2018
				Rifampicin, Isoniazid, Pyrazinamide, Etambutol, Levofloxacin, Terizidone