rifampin and acetylisoniazid

rifampin has been researched along with acetylisoniazid* in 4 studies

Trials

1 trial(s) available for rifampin and acetylisoniazid

ArticleYear
Low serum concentrations of anti-tuberculosis drugs and determinants of their serum levels.
    The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2007, Volume: 11, Issue:9

    Low serum concentrations of anti-tuberculosis drugs have occasionally been associated with treatment failure.. To determine the prevalence of low serum concentrations of anti-tuberculosis drugs and to identify the determinants of drug concentrations.. Venous blood was obtained 2 h after drug ingestion, and serum levels of isoniazid (INH), rifampicin (RMP), ethambutol (EMB), pyrazinamide (PZA), acetyl INH and 25-desacetyl RMP were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Patients with human immunodeficiency virus co-infection and gastrointestinal disease or diarrhoea were excluded.. Among 69 enrolled TB patients, the prevalence of a low 2 h serum concentration of at least one anti-tuberculosis drug was 46.4%. Prevalences of a low concentration of INH, RMP, EMB or PZA were 15.2%, 23.5%, 22.4% and 4.5%, respectively. By multivariate linear regression analysis, the serum concentrations of INH, RMP and PZA were positively associated with dose per kg of body weight (P < 0.05). Moreover, INH concentration was associated with acetyl INH/INH ratio (beta = -8.588, P < 0.001) and EMB concentration was associated with calculated creatinine clearance (beta = -0.025, P < 0.001).. Low concentrations of anti-tuberculosis drugs are common, and although the clinical significance of low concentrations remains uncertain, it may be necessary to optimise drug doses by therapeutic drug monitoring, especially in patients with an inadequate clinical response to chemotherapy.

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antitubercular Agents; Chromatography, Liquid; Drug Monitoring; Ethambutol; Female; Humans; Isoniazid; Linear Models; Male; Mass Spectrometry; Middle Aged; Pyrazinamide; Rifampin; Tuberculosis

2007

Other Studies

3 other study(ies) available for rifampin and acetylisoniazid

ArticleYear
Development and validation of liquid chromatography tandem mass spectrometry method for simultaneous quantification of first line tuberculosis drugs and metabolites in human plasma and its application in clinical study.
    Journal of pharmaceutical and biomedical analysis, 2015, Volume: 102

    Rifampicin (RIF) and isoniazid (INH), first line drugs for the treatment of tuberculosis, are known to cause hepatotoxicity as a serious adverse side effect. To further understand the pharmacokinetic parameters of these two drugs, we have developed and validated a rapid, sensitive and selective LC-MS/MS method for simultaneous quantification of RIF, INH and their metabolites 25-desacetylrifampicin (DRIF), acetylisoniazid (AcINH) and isonicotinic acid (INA). Analytes were extracted from 20 μl of plasma using solid-phase extraction (SPE) followed by chromatographic separation on Zorbax SB-Aq column (50 mm × 4.6mm, particle size 5 μm) using stepwise gradient elution of 5mM ammonium acetate and 90% acetonitrile with 0.1% formic acid. Separation of all analytes was achieved in the total run time of 6 min. The analytes were detected under positive ionization mode by multiple reaction monitoring (MRM) and quantification of analytes was performed by using deuterium-labelled internal standard. Excellent linearity (r(2) ≥ 0.995) was achieved for the analytes at different concentration ranges. The method was accurate (90-115%), precise (CV %<14) and specific. Matrix effect was in the range of 93-111% except for INA (40-42%) while recovery from SPE was reproducible (CV %<7.4) in the range of 60-86%. Post-preparative stability (48 h, 6°C autosampler) and freeze-thaw stability (3 cycles) were assessed with mean recovered concentration of >85%. The method was successfully applied to a clinical study of 33 healthy subjects to evaluate the effect of concomitant of INH on the pharmacokinetic parameters of RIF as well as the segregation of the subjects into slow or fast acetylators of INH.

    Topics: Antitubercular Agents; Chromatography, High Pressure Liquid; Humans; Isoniazid; Rifampin; Solid Phase Extraction; Tandem Mass Spectrometry

2015
Simultaneous determination of isoniazid, pyrazinamide, rifampicin and acetylisoniazid in human plasma by high-performance liquid chromatography.
    Analytical sciences : the international journal of the Japan Society for Analytical Chemistry, 2010, Volume: 26, Issue:11

    A sensitive and accurate high-performance liquid-chromatography method was developed and validated for the simultaneous determination of pyrazinamide (PZA), isoniazid (INH), rifampicin (RFP) and acetylisoniazid (AcINH) in human plasma. Separation was performed on a Max-RP C(12) column using gradient elution and a flow-rate program. The mobile phase was methanol-acetonitrile-buffer (20 mM of heptanesulfonic acid sodium, pH 2.5) with a ratio of 10:8:82 (v/v/v) at the initial phase. All calibration curves had good linearity (r(2) > 0.99) between the test ranges. The intra- and inter-day precision was less than 8.8% in good accuracy (<15%). The limit of detection with a signal-to-noise (S/N) of 3 was 0.014, 0.009, 0.023 and 0.054 µg mL(-1) for PZA, AcINH, INH and RFP, respectively. The method was selective, sensitive and reliable, and is a good alternative for routine therapeutic drug monitoring of the four compounds during the treatment of tuberculosis patients.

    Topics: Calibration; Chromatography, High Pressure Liquid; Humans; Isoniazid; Pyrazinamide; Rifampin; Sensitivity and Specificity

2010
Simultaneous determination of first-line anti-tuberculosis drugs and their major metabolic ratios by liquid chromatography/tandem mass spectrometry.
    Rapid communications in mass spectrometry : RCM, 2007, Volume: 21, Issue:7

    Monitoring of anti-tuberculosis drug concentrations and dose adjustment can be helpful in cases that show poor response to treatment. Here, we describe a method that can rapidly and simultaneously measure the blood concentrations of four anti-tuberculosis drugs (isoniazid, rifampicin, pyrazinamide, and ethambutol) and two major metabolic ratios (acetylisoniazid/isoniazid and 25-desacetylrifampicin/rifampicin) using high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). A C18 reversed-phase column and gradients of methanol in 0.3% formic acid and water were used for HPLC separation. The drug concentrations were determined by multiple reaction monitoring in positive ion mode and the assay performance was evaluated. We determined peak concentration ranges for each drug and acetylisoniazid/isoniazid and 25-desacetylrifampicin/rifampicin ratios by analyzing 2-h post-dose samples in patients treated with standard dosing as a first-line treatment. The preparation of 20 samples including two steps of deproteinization with 50% and 100% methanol was performed within 20 min and chromatographic separation was achieved within 4 min/sample. Interassay calibration variability data obtained over concentrations of 0-8 microg/mL for isoniazid and ethambutol and 0-80 microg/mL for rifampicin and pyrazinamide showed a linear and reproducible curve. Within-run and between-run imprecision (CVs) were 1.9-5.5% and 3.5-10.5% and the lower limits of detection and quantification were 0.01-0.5 microg/mL and 0.05-1.0 microg/mL, respectively. The isoniazid concentration was found to be inversely correlated to the acetylisoniazid/isoniazid ratio (R=-0.739, P<0.001). The devised method allows for the simple, rapid, sensitive and reproducible quantification of isoniazid, rifampicin, pyrazinamide, ethambutol and their two metabolic ratios and should be helpful for therapeutic drug monitoring in tuberculosis patients.

    Topics: Antitubercular Agents; Blood Chemical Analysis; Chromatography, High Pressure Liquid; Complex Mixtures; Humans; Isoniazid; Rifampin; Spectrometry, Mass, Electrospray Ionization

2007