SEARCH · Search PubMed

Results for “PYRAZINAMIDE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,027 records · Page 57Linked to original sources

PubMed2003

Nanoparticle encapsulated antitubercular drugs as a potential oral drug delivery system against murine tuberculosis.

Patient non-compliance is the major drawback associated with the long-duration chemotherapy of tuberculosis (TB); hence, reduction in dosing frequency forms an important therapeutic strategy. The present study reports the formulation of three frontline antitubercular drugs (ATD), i.e. rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) encapsulated in poly (DL-lactide-co-glycolide) (PLG) nanoparticles. Drug encapsulation efficiencies were 56.9+/-2.7% for RIF, 66.3+/-5.8% for INH and 68+/-5.6% for PZA. Following a single oral administration of these preparations to mice, the drugs could be detected in the circulation for 6 days (RIF) and 9 days (INH/PZA), whereas therapeutic concentrations in the tissues were maintained for 9-11 days. Further, on oral administration of drug-loaded nanoparticles to Mycobacterium tuberculosis-infected mice at every 10th day, no tubercle bacilli could be detected in the tissues after 5 oral doses of treatment. Therefore, nanoparticle-based ATD therapy forms a sound basis for reduction in dosing frequency for better management of TB.

Administration, Oral↗

PubMed2005

Solid lipid particle-based inhalable sustained drug delivery system against experimental tuberculosis.

The present study was planned to evaluate the chemotherapeutic potential of nebulized solid lipid particles (SLPs) incorporating rifampicin, isoniazid and pyrazinamide against experimental tuberculosis. The SLPs prepared by the "emulsion solvent diffusion" technique possessed a favourable mass median aerodynamic diameter suitable for bronchoalveolar drug delivery. Following a single nebulization to guinea pigs, therapeutic drug concentrations were maintained in the plasma for 5 days and in the organs (lungs, liver and spleen) for 7 days whereas free drugs were cleared by 1-2 days. The mean residence time and drug bioavailability were improved several-fold in the case of drug-loaded SLPs. A similar pharmacokinetic profile was observed in Mycobacterium tuberculosis-infected guinea pigs. On nebulization of drug-loaded SLPs to infected guinea pigs at every 7th day, no tubercle bacilli could be detected in the lungs/spleen after 7 doses of treatment whereas 46 daily doses of orally administered drugs were required to obtain an equivalent therapeutic benefit. Further, there was no evidence of any biochemical hepatotoxicity. Thus, nebulization of SLP-based antitubercular drugs forms a sound basis for improving drug bioavailability and reducing the dosing frequency for better management of pulmonary tuberculosis.

Administration, Inhalation↗

PubMed1997

New horizons in the treatment of tuberculosis.

The development of new chemotherapy for the treatment of tuberculosis has three major objectives: first, the development of faster-acting drugs to shorten the duration of treatment; second, the development of novel antimicrobials to counter the emergence of bacteria resistant to current therapies; and, third, the development of chemotherapeutics that specifically target dormant bacilli to treat the one-third of the world's population latently infected with tubercle bacilli. Strategies based upon optimizing the inhibition of known targets require an extensive knowledge of the detailed mechanism of action of current antimycobacterial agents. For many agents such as isoniazid, ethambutol, rifampin, and pyrazinamide such knowledge is now available. Strategies based upon the identification of novel targets will necessitate the identification of biochemical pathways specific to mycobacteria and related organisms. Many unique metabolic processes occur during the biosynthesis of mycobacterial cell wall components, and some attractive new targets have emerged. The development of targets specific to latency will require a detailed picture of the metabolism and biochemical pathways occurring in dormant bacilli. Recent evidence suggests that anaerobic metabolic pathways may operate in dormant bacilli, and the enzymes involved in such pathways may also provide significant new targets for intervention. The combination of the mycobacterial genome sequence that is anticipated to become available this year with an improved understanding of the unique metabolic processes that define mycobacteria as a genus offers the greatest hope for the elimination of one of mankind's oldest enemies.

Animals↗

PubMed1980

Hereditary renal hypouricemia. Isolated tubular defect of urate reabsorption.

A consanguineous Iraqi Jewish kindred is presented in which asymptomatic and apparently benign hypouricemia, secondary to an isolated renal defect, segregates as an autosomal recessive trait affecting four of eight siblings. The 8-year-old proband was ascertained during an evaluation for an apparently unrelated inherited neurologic disorder with which an older normouricemic sibling was also affected. Urate clearance in three affected siblings was 22.6, 35.2, and 60.8 ml/minute, while that in normouricemic siblings was 8.6 to 10.6 ml/minute. Pyrazinamide administration to one affected sibling reduced the urate clearance from 61 to 14.7 ml/minute. A recessively inherited single gene lesion producing a tubular defect is postulated; the exact site(s) is uncertain.

Adolescent↗

PubMed1984

The treatment of urinary tuberculosis.

During the last 7 years we treated 92 patients with tuberculosis of the urinary tract. Patients with tuberculous infection were divided into 3 groups according to treatment: group 1--no surgical treatment (18 patients), group 2--ablative surgery (45 patients) and group 3--reconstructive surgery (29 patients). Antituberculous drugs, consisting of rifampin, pyrazinamide, isoniazid and ethambutol, were given according to the severity and extent of the infection process. The results of medical and surgical treatment were most gratifying. Surgical morbidity was low and there was no immediate mortality.

Adult↗

PubMed1976

A case of uric acid renal stone with hypouricemia caused by tubular reabsorptive defect of uric acid.

A 60-year-old man had a uric acid stone in the kidney and laboratory findings of hypouricemia (1.1 mg. per 100 ml.) and increased uric acid clearance (43 ml. per minute per 1.73 m.2). Clearance of uric acid exceeded the endogenous creatinine clearance after administration of pyrazinamide, an inhibitor of renal tubular secretion of uric acid. It was suggested that our patient had a complete defective mechanism for uric acid reabsorption, resulting in hyperuricuria and the formation of the uric acid stone.

Creatinine↗

PubMedDate not supplied

Resistance to antituberculosis drugs in rural South Africa: rates, patterns, risks, and transmission dynamics.

This study describes the rate, pattern, and transmission dynamics of, and risk factors for, isolates of Mycobacterium tuberculosis resistant to antituberculosis drugs in a rural South African health district. Twenty-one of 254 (7.6%; 95% confidence interval [CI] 4.8-11.4) isolates from incident cases were resistant to at least one drug (isoniazid, rifampicin, streptomycin, ethambutol). A random sample of 28 otherwise susceptible isolates and all 21 resistant isolates were susceptible to pyrazinamide. There was one case of combined isoniazid/rifampicin resistance. The rate of initial resistance was 8.1% (95% CI 4.9-12.4) and of acquired resistance 6.2% (95% CI 1.9-14.2). Age, sex, known human immunodeficiency virus status, and previous treatment history were not associated with drug resistance. Restriction fragment length polymorphism (RFLP) analysis of 13 of the 21 resistant specimens showed 12 different banding patterns. Rates of drug resistance were low in this representative sample of patients from a defined geographical area. Previous treatment history was probably not a risk factor because of the use of multiple drug regimens, directly observed therapy, and high completion rates in those previously treated. Although limited in number, the RFLP data suggested that recent local transmission of resistant strains was not occurring to a significant extent.

Adult↗

PubMedDate not supplied

Directly observed therapy for tuberculosis given twice weekly in the workplace in urban South Africa.

Effective models of delivery of directly observed therapy (DOT) for tuberculosis in resource-poor settings are needed. Intermittent chemotherapy may be an important component of DOT delivered in the community as it means fewer visits to supervisors. There is no published evidence on the efficacy of twice weekly therapy given from the start of treatment without an intensive daily phase. We analysed data from 3 large cohort studies in a migrant, urban workforce in South Africa between 1975 and 1983. All patients received 4 drugs (isoniazid, rifampicin, pyrazinamide and streptomycin) twice weekly under direct observation by a nurse in the workplace. Of 444 patients, 378 (85.1%) completed treatment. Cure could be assessed in 362, and 348 (96.1%, 95% confidence interval 93.7-97.8%) were bacteriologically cured. Sputum status was assessed at 2-3 months in 343 patients and 309 (90.1%) were sputum negative. Eighteen patients relapsed (5.7%; 2.9/100 patient-years of observation). DOT can be effectively delivered to a migrant, urban workforce, and 4-drug therapy given twice weekly under direct observation is efficacious.

Adult↗

PubMedDate not supplied

Two 8-month regimens of chemotherapy for treatment of newly diagnosed pulmonary tuberculosis: international multicentre randomised trial.

BACKGROUND: A WHO-recommended 8-month regimen based on ethambutol and isoniazid was evaluated in a randomised clinical trial against a 6-month standard regimen. METHODS: 1355 patients with newly diagnosed smear-positive pulmonary tuberculosis were randomly assigned one of three regimens: daily ethambutol, isoniazid, rifampicin, and pyrazinamide for 2 months, followed by ethambutol and isoniazid for 6 months (2EHRZ/6HE); the same drugs but given three times weekly in the initial intensive phase (2[EHRZ]3/6HE); or the same initial intensive phase as the first regimen, followed by 4 months of daily rifampicin and isoniazid (2EHRZ/4HR). Follow-up was to 30 months after the start of chemotherapy. Sputum was regularly examined by microscopy and culture. Unfavourable outcome was defined as failure during treatment or relapse afterwards. Analyses were by intention to treat. FINDINGS: At 2 months, a significantly higher proportion of patients assigned the daily intensive phase than of those assigned the three-times-weekly regimen were culture negative (700/828 [85%] vs 333/433 [77%], p=0.001). 12 months after the end of chemotherapy, the proportions of unfavourable outcomes were 36 of 346 (10%) with 2EHRZ/6HE, 48 of 351 (14%) with 2(EHRZ)3/6HE, and 17 of 347 (5%) with 2EHRZ/4HR. Both 8-month regimens were significantly inferior to the control 6-month standard regimen (difference between control and 2EHRZ/6HE 5.5% [95% CI 1.6 to 9.4]; between control and 2(EHRZ)3/6HE 8.8% [4.5 to 13.0]). Adverse effects leading to interruption of treatment for 7 days or longer occurred in 28 patients (12 2EHRZ/6HE, five 2[EHRZ]3/6HE, 11 2EHRZ/4HR). INTERPRETATION: The results of this study must be taken into account in recommendations on management of new cases of smear-positive tuberculosis.

Adolescent↗

PubMed1994

Randomised trial of thiacetazone and rifampicin-containing regimens for pulmonary tuberculosis in HIV-infected Ugandans. The Makerere University-Case Western University Research Collaboration.

Among HIV-positive patients who received treatment for active tuberculosis, thiacetazone has been associated with cutaneous hypersensitivity and recurrent tuberculosis. No controlled trials have investigated the safety and efficacy of thiacetazone-containing regimens compared with alternative regimens among patients with HIV. In a randomised clinical trial of 191 HIV-positive patients with active pulmonary tuberculosis, we examined the safety and short-term efficacy of isoniazid, rifampicin, and pyrazinamide for two months followed by isoniazid and rifampicin for seven months (RHZ) compared with streptomycin, thiacetazone, and isoniazid for two months followed by thiacetazone and isoniazid for ten months (STH). Between May, 1990, and September, 1991, 191 HIV-positive adult Ugandan patients with acid-fast bacilli sputum smear-positive pulmonary tuberculosis (93% confirmed by culture) received either STH or RHZ. Subjects had a standard evaluation that included Mantoux skin test, complete blood count with differential white blood cell count, and chest radiography. After starting therapy, subjects were followed-up over one year for three outcomes: complications of anti-tuberculosis therapy, early sterilisation of cultures, and survival. Of 191 eligible subjects, 90 received STH and 101 received RHZ. The overall one-year survival was similar for STH and RHZ (65% vs 72%), but when controlled for baseline differences in Mantoux reaction size and absolute lymphocyte count, the relative risk of death for STH compared with RHZ was 1.57 (95% CI 1.0-2.48). Overall, 12 adverse drug reactions occurred in the STH arm (18.2 reactions per 100 person years [PYO]) compared with one in the RHZ arm (1.6 reactions per 100 PYO) for a relative risk of 11.7 (95% CI 1.52-90.0). 10 cutaneous reactions occurred in the STH arm (15.2 events per 100 PYO) compared with one event in the RHZ arm (1.6 events per 100 PYO) for a relative risk of 9.7 (95% CI: 1.24, 75.8). A greater proportion of RHZ patients compared with STH patients had sterilised their sputum within two months (74% vs 37%, p < 0.001). In developing countries, rifampicin-containing regimens should be given, when possible, to HIV-positive patients to reduce drug toxicity and to prolong survival.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

[Randomized trial of three regimens to prevent tuberculosis in HIV-infected patients with anergy].

INTRODUCTION: To evaluate the efficacy of three regimens of prophylactic therapy for tuberculosis in HIV-infected patients with anergy. METHODS: Prospective, multi-center, randomized, comparative, and open clinical trial. Anergy was defined as absence of induration in response to three antigens (PPD, Candida albicans and parotiditis antigen) applied by the Mantoux method. Patients were randomized into one of the following prophylactic treatment groups: isoniazid for six months (6H), rifampin plus isoniazid for three months (3RH), rifampin plus pyrazinamide for two months (2RZ) or no treatment (NT). After completion of treatment, patients were followed up for two years. RESULT: A total of 319 patients were included in the study, 83 in the 6H regimen, 82 in 3RH, 77 in 2RZ and 77 in NT. The observation period following treatment was 88, 96, 81 and 126 person-years, respectively, for 6H, 3RH, 2RZ and NT. There were 11 cases of tuberculosis during the follow-up period. The tuberculosis rates (cases per 100 person-years) were 3.4, 3.1, 1.2 and 3.1 for 6H, 3RH, 2RZ and NT respectively, with relative risks in regimens 6H, 3RH and 2RZ with respect to NT of 1.07 (0.24-4.80), 0.98 (0.22-4.4) and 0.39 (0.04-3.48), all statistically non-significant. Twenty-nine patients died during the follow-up period, none due to tuberculosis, and no appreciable differences were found among the groups. CONCLUSIONS: The results showed no significant decrease in the risk of developing tuberculosis with any of the evaluated regimens and, therefore, do not support the use of antituberculosis chemoprophylaxis in anergic HIV-infected patients.

Adult↗

PubMed2001

Normouricemia in the syndrome of inappropriate antidiuretic hormone secretion.

Hyponatremia is seen in 40% to 60% of hospitalized acquired immune deficiency syndrome (AIDS) patients. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) and volume contraction are the most common causes. The serum uric acid level can be used to distinguish between these two causes of hyponatremia. Hypouricemia is the rule in SIADH, whereas hyperuricemia commonly accompanies volume contraction. This report presents an AIDS patient with SIADH and normouricemia secondary to pyrazinamide and ethambutol.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Cholangiocarcinoma and severe renal hypouricemia: a study of the renal mechanisms.

Hypouricemia in malignant neoplasms is rarely reported. We present a previously unreported case of cholangiocarcinoma associated with severe persistent hypouricemia (serum uric acid levels ranged from 0.07 to 0.08 mmol/L [1.16 to 1.40 mg/100 mL], and increased urate clearance (50.90 to 57.33 mL/min v a mean value in 20 normal subjects of 9.75 +/- 1.65 mL/min). High fractional urate clearance (Cus/Ccr = 0.50 to 0.58 v 0.09 +/- 0.01 in normals) was suppressed only slightly following pyrazinamide (PZA), to 0.29 versus 0.007, and was surprisingly enhanced by probenecid (PB) to 1.78 versus 0.63 in normals. No other renal tubular or metabolic abnormalities were detected. This previously unreported association of a high PZA-nonsuppressible urate excretion with a postprobenecid urate clearance exceeding glomerular filtration rate suggests that a combined renal tubular defect is responsible for hypouricemia. The patient described here provides evidence to support the presence of a presecretory reabsorptive defect in association with a "relatively high" urate secretion by the renal tubule. This report adds to the list of hypouricemic conditions and presents an important clue to elucidate urate handling mechanisms in man.

Adenoma, Bile Duct↗

PubMedDate not supplied

[Study of primary resistance to antitubercular drugs in Galicia].

The primary resistance of 100 specimens of Mycobacterium tuberculosis isolated in patients with active tuberculosis confirmed bacteriologically was studied prospectively over a period of 15 months. Strains resistant to 1 or more drugs were found in 5 patients. Three patients presented resistance to 2 drugs (isoniazide and streptomycin in 2 and rifampicin and isoniazid, streptomycin and ethambutol); and the fifth was resistant only to pyrazinamide. Owing to the few instances of primary resistance found, it was impossible to establish whether any of the factors analyzed in each patient was related to a higher index of resistance, although 4 of the 5 resistant strains came from respiratory specimens. We conclude that the index of primary resistance in our area is low and this allows us to do without prescribing a fourth drug in the first two months of anti-tuberculosis therapy, and makes routine sensitivity tests unnecessary for patients with no history of prior treatment for tuberculosis.

Antitubercular Agents↗

PubMed2001

Ion interaction reagent reversed-phase high-performance liquid chromatography determination of anti-tuberculosis drugs and metabolites in biological fluids.

New methods of ion interaction reagent (IIR) RP-HPLC are presented for the determination of anti-tuberculosis drugs and their metabolites, singly or in multi-component mixtures, in biological fluids. The following analytes are considered: isoniazid, ethionamide, pyrazinamide, morphazinamide, p-aminosalicylic acid, nicotinic and isonicotinic acids. Aqueous solutions of three different ion interaction reagents are alternatively or comparatively used as the mobile phases, namely: (A) 5.00 mM octylamine at pH 3.00 for o-phosphoric acid, (B) 5.00 mM octylamine at pH 8.00 for o-phosphoric acid, and (C) 5.00 mM 1,6 diaminohexane at pH 6.00 for o-phosphoric acid. The response linearity between peak area and analyte concentration is verified for all the analytes in the concentration range within the determination limits and 2.00 mg/l. Detection limits are always lower than 82 microg/l for standard solutions; in the analysis of samples of rat serum, rat plasma and human serum, the matrix effect is negligible, the detection limits are always lower than 94 microg/l and the average recovery yield is always greater than 96%.

Aminosalicylic Acid↗

PubMed2002

Behavior of uptake of moisture by drugs and excipients under accelerated conditions of temperature and humidity in the absence and the presence of light. 1. Pure anti-tuberculosis drugs and their combinations.

An investigation was carried out to determine the behavior of moisture gain by four anti-tuberculosis drugs, viz. rifampicin, isoniazid, pyrazinamide and ethambutol, when exposed in pure form and in combinations to accelerated conditions of 40 degrees C and 75% RH, in the absence and the presence of light. Weight gain was seen only in those samples that contained ethambutol, and this behavior was observed both in dark and lighted chambers. There was a decrease in moisture uptake with an increase in the number of drugs in the mixture. Another observation was a higher weight gain by the mixture of ethambutol and isoniazid in a dark chamber, than either pure ethambutol or drug combinations containing ethambutol. The most interesting finding was an overall acceleration of weight gain in the presence of light as compared with dark conditions, which is a hitherto unknown phenomenon.

Adsorption↗

PubMed2001

Increasing resistance of M. tuberculosis to anti-TB drugs in Saudi Arabia.

The incidence of drug resistance in Mycobacterium tuberculosis (MTB) isolated from our hospital between April 1996 and March 1998 was compared with an earlier study (1993-1995). Thirty (29.7%) of 101 MTB isolates were resistant to one or more anti-TB drugs and 21 (20%) of 101 were multi-drug resistant M. tuberculosis (MDR-TB). Resistance was most common to isoniazid (28.7%), followed by streptomycin (22.8%) and rifampicin (20.8%). Resistance to pyrazinamide and ethambutol was 7.9 and 6.9%, respectively. There was a three-fold increase in resistance compared with the earlier study.

Antitubercular Agents↗

PubMed2003

The decline of high drug resistance rate of pulmonary Mycobacterium tuberculosis isolates from a southern Taiwan medical centre, 1996-2000.

To investigate the anti-tuberculosis drug resistance pattern of pulmonary tuberculosis isolates in southern Taiwan, we performed a hospital-based surveillance at a southern Taiwan medical centre from 1996 to 2000. The combined drug resistance rates to at least one of four first-line agents (isoniazid, rifampicin, ethambutol, streptomycin) was 52.4%, and to both isoniazid and rifampicin was 11.4%, indicating high resistance rates compared with those reported in the World Health Organization (WHO)/International Union Against Tuberculosis and Lung Disease (IUATLD) global project and in northern Taiwan. The resistance rates to two second-line drugs, cycloserine, and kanamycin, were 75.7 and 23.7%, respectively. A significant decreasing trend in resistance rates to all tested drugs except streptomycin was observed during the 5-year period. The resistance rates in 1996 and 2000 were 43.1 and 16.4% for isoniazid, 23.4 and 9.5% for rifampicin, 23.4 and 12.1% for ethambutol, 92.7 and 50.9% for pyrazinamide. The combined drug resistance rate may not be the most accurate tool as it includes previously treated cases that may inflate the resistance rate and cases without a history of treatment. However, the observation of trends in the susceptibility of pulmonary tuberculosis with the increasing percentages of tuberculosis patients receiving the complete treatment course and the decreasing percentages of cases lost to follow-up in Kaohsiung after the institution of new governmental regulations for case management in 1997, suggest that such intervention programs are useful.

Antitubercular Agents↗