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Tubercle Sep 1988A case of thrombocytopenia caused by pyrazinamide is reported in a patient receiving chemotherapy for pulmonary tuberculosis.
A case of thrombocytopenia caused by pyrazinamide is reported in a patient receiving chemotherapy for pulmonary tuberculosis.
Topics: Adult; Humans; Male; Pyrazinamide; Thrombocytopenia; Tuberculosis, Pulmonary
PubMed: 3254638
DOI: 10.1016/0041-3879(88)90026-8 -
Revue de Pneumologie Clinique 2015The aim of this article is to give practicing physicians a practical approach to the treatment of latent and active tuberculosis. Most patients follow TB standard... (Review)
Review
The aim of this article is to give practicing physicians a practical approach to the treatment of latent and active tuberculosis. Most patients follow TB standard treatment recommended by WHO that depend on category of patient. It is a combination of four essential tuberculosis drugs of the first group: isoniazid, rifampicin, pyrazinamid and ethambutol; in some cases streptomycin can replace ethambutol. This initial phase of intensive treatment is followed by a consolidation phase. Drugs should be administered in the morning on an empty stomach one hour before meals. Treatment of latent tuberculosis (TB) infection is an important component of TB control programs. Preventive treatment can reduce the risk of developing active TB.
Topics: Antitubercular Agents; Drug Therapy, Combination; Ethambutol; Humans; Isoniazid; Latent Tuberculosis; Practice Guidelines as Topic; Pyrazinamide; Rifampin; Treatment Outcome; Tuberculosis; Tuberculosis, Pulmonary; World Health Organization
PubMed: 25434510
DOI: 10.1016/j.pneumo.2014.09.001 -
The American Review of Respiratory... Jul 1981To investigate whether pyrazinamide deamidase activity is suppressed in tuberculosis, serial serum concentrations of pyrazinamide, following 40 mg of pyrazinamide per... (Clinical Trial)
Clinical Trial
To investigate whether pyrazinamide deamidase activity is suppressed in tuberculosis, serial serum concentrations of pyrazinamide, following 40 mg of pyrazinamide per kg, were determined in 10 patients with sputum positive pulmonary tuberculosis and in 10 control subjects without disease. The concentrations and the half-lives of pyrazinamide were similar in the 2 groups, suggesting no suppression of the deamidase activity in tuberculous patients.
Topics: Antitubercular Agents; Clinical Trials as Topic; Drug Evaluation; Humans; Pyrazinamide; Random Allocation; Tuberculosis, Pulmonary
PubMed: 7020509
DOI: 10.1164/arrd.1981.124.1.97 -
Antimicrobial Agents and Chemotherapy Dec 2022A critical barrier to codevelopment of tuberculosis (TB) regimens is a limited ability to identify optimal drug and dose combinations in early-phase clinical testing....
A critical barrier to codevelopment of tuberculosis (TB) regimens is a limited ability to identify optimal drug and dose combinations in early-phase clinical testing. While pharmacokinetic-pharmacodynamic (PKPD) target attainment is the primary tool for exposure-response optimization of TB drugs, the PD target is a static index that does not distinguish individual drug contributions to the efficacy of a multidrug combination. A PKPD model of bedaquiline-pretomanid-pyrazinamide (BPaZ) for the treatment of pulmonary TB was developed as part of a dynamic exposure-response approach to regimen development. The model describes a time course relationship between the drug concentrations in plasma and their individual as well as their combined effect on sputum bacillary load assessed by solid culture CFU counts and liquid culture time to positivity (TTP). The model parameters were estimated using data from the phase 2A studies NC-001-(J-M-Pa-Z) and NC-003-(C-J-Pa-Z). The results included a characterization of BPaZ activity as the most and least sensitive to changes in pyrazinamide and bedaquiline exposures, respectively, with antagonistic activity of BPa compensated by synergistic activity of BZ and PaZ. Simulations of the NC-003 study population with once-daily bedaquiline at 200 mg, pretomanid at 200 mg, and pyrazinamide at 1,500 mg showed BPaZ would require 3 months to attain liquid culture negativity in 90% of participants. These results for BPaZ were intended to be an example application with the general approach aimed at entirely novel drug combinations from a growing pipeline of new and repurposed TB drugs.
Topics: Humans; Pyrazinamide; Antitubercular Agents; Diarylquinolines; Tuberculosis, Pulmonary; Nitroimidazoles; Tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 36377952
DOI: 10.1128/aac.00898-22 -
Nature Medicine Jun 1996
Topics: Amidohydrolases; Animals; Antitubercular Agents; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Humans; Mice; Pyrazinamide; Tuberculosis
PubMed: 8640549
DOI: 10.1038/nm0696-635 -
Nature Medicine Sep 2000Tuberculosis treatment is shortened to six months by the indispensable addition of pyrazinamide (PZA) to the drug regimen that includes isoniazid and rifampin. PZA is a...
Tuberculosis treatment is shortened to six months by the indispensable addition of pyrazinamide (PZA) to the drug regimen that includes isoniazid and rifampin. PZA is a pro-drug of pyrazinoic acid (POA) (ref. 3), whose target of action has never been identified. Although PZA is active only against Mycobacterium tuberculosis, the PZA analog 5-chloro-pyrazinamide (5-Cl-PZA) displays a broader range of anti-mycobacterial activity. We have found that the eukaryotic-like fas1 gene (encoding fatty acid synthetase I, FASI) from M. avium, M. bovis BCG or M. tuberculosis confers resistance to 5-Cl-PZA when present on multi-copy vectors in M. smegmatis. 5-Cl-PZA and PZA markedly inhibited the activity of M. tuberculosis FASI, the biosynthesis of C16 to C24/C26 fatty acids from acetyl-CoA (ref. 6). Importantly, PZA inhibited FASI in M. tuberculosis in correlation with PZA susceptibility. These results indicate that FASI is a primary target of action for PZA in M. tuberculosis. Further characterization of FASI as a drug target for PZA may allow the development of new drugs to shorten the therapy against M. tuberculosis and may provide more options for treatment against M. bovis, M. avium and drug resistant M. tuberculosis.
Topics: Animals; Antitubercular Agents; Bacterial Proteins; Enzyme Inhibitors; Fatty Acid Synthases; Humans; Mycobacterium tuberculosis; Prodrugs; Pyrazinamide; Tuberculosis, Pulmonary
PubMed: 10973326
DOI: 10.1038/79558 -
PloS One 2014In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in the dose delivery and drug exposure. There is no...
SETTING
In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in the dose delivery and drug exposure. There is no data on the quality of first-line drugs content in split fixed-dose combination tablets.
OBJECTIVE
To determine Isoniazid, Pyrazinamide and Rifampicin content uniformity in split FDC tablets used in the treatment of childhood tuberculosis.
DESIGN
Drug contents of 15 whole tablets, 30 half tablets and 36 third tablets were analysed by high performance liquid chromatography. The content uniformity was assessed by comparing drug content measured in split portions with their expected amounts and the quality of split portions was assessed applying qualitative specifications for whole tablets.
RESULTS
All whole tablets measurements fell into the USP proxy for the three drugs. But a significant number of half and third portions was found outside the tolerated variation range and the split formulation failed the requirements for content uniformity. To correct for the inaccuracy of splitting the tablets into equal portions, a weight-adjustment strategy was used but this did not improve the findings.
CONCLUSION
In split tablets the content of the three drugs is non-uniform and exceeded the USP recommendations. There is an absolute need to make child-friendly formulations available for the treatment of childhood tuberculosis.
Topics: Chemistry, Pharmaceutical; Drug Combinations; Humans; Isoniazid; Pyrazinamide; Quality Control; Rifampin; Tablets; Tuberculosis, Pulmonary
PubMed: 25004128
DOI: 10.1371/journal.pone.0102047 -
A simplified pyrazinamidase test for pyrazinamide drug susceptibility in Mycobacterium tuberculosis.Journal of Microbiological Methods Nov 2018We modified Wayne's pyrazinamidase test against Mycobacterium tuberculosis to indirectly measure pyrazinamidase activity via pyrazinoic acid in liquid medium. The...
We modified Wayne's pyrazinamidase test against Mycobacterium tuberculosis to indirectly measure pyrazinamidase activity via pyrazinoic acid in liquid medium. The modified pyrazinamidase test was easy to perform and its results were in complete agreement with those of the conventional Wayne's method, highlighting its potential application in phenotypic pyrazinamide susceptibility testing.
Topics: Amidohydrolases; Antitubercular Agents; Culture Media; Diagnostic Tests, Routine; Drug Resistance, Bacterial; Enzyme Assays; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Pyrazinamide; Sensitivity and Specificity
PubMed: 30316980
DOI: 10.1016/j.mimet.2018.09.018 -
ChemMedChem Apr 2012
Topics: Amidohydrolases; Antitubercular Agents; Humans; Mycobacterium tuberculosis; Pyrazinamide; Tuberculosis
PubMed: 22241617
DOI: 10.1002/cmdc.201100587 -
International Archives of Allergy and... 2012Pyrazinamide (PZA), an antituberculosis drug, may cause hypersensitivity reactions. Here, we report a case of anaphylaxis secondary to a PZA administration for...
Pyrazinamide (PZA), an antituberculosis drug, may cause hypersensitivity reactions. Here, we report a case of anaphylaxis secondary to a PZA administration for tuberculosis pleuritis. To the best of our knowledge, this is the first reported case of strongly possible IgE-mediated, PZA-induced anaphylaxis proved by skin prick test and oral provocation/desensitization.
Topics: Adult; Anaphylaxis; Antitubercular Agents; Desensitization, Immunologic; Female; Humans; Pyrazinamide; Skin Tests
PubMed: 21986254
DOI: 10.1159/000327537