Serum drug concentrations of INH and RMP predict 2-month sputum culture results in tuberculosis patients

Mah, Allison; Kharrat, Houssam Al; Ahmed, Rabia; Gao, Zhijun; Der, Evelina; Hansen, E; Long, Richard; Kunimoto, Dennis; Cooper, Ryan

doi:10.5588/ijtld.14.0405

Cited by 23 publications

(19 citation statements)

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“…Notwithstanding the benefit of TDM of anti-TB drugs is still to be established, drug monitoring may be of value as a tool to assess whether inadequate response to treatment can be attributed to suboptimal exposure to anti-TB drugs. In case of delayed sputum culture conversion, for example, 2 months sputum culture positivity, as well as in case of relapsing TB, monitoring anti-TB plasma drug concentrations may be particular relevant (11,12,32). Low plasma concentrations can result from malabsorption and in case of HIV-infection, gastrointestinal anomalies, malnutrition, diabetes or renal or hepatic dysfunction, it may also be relevant to apply drug monitoring (2,4,9,16,(33)(34)(35).…”

Section: Resultsmentioning

confidence: 99%

Simultaneous quantification of isoniazid, rifampicin, ethambutol and pyrazinamide by liquid chromatography/tandem mass spectrometry

Prahl

Lundqvist

Bahl

et al. 2016

APMIS

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A remediable cause of poor treatment response in drug-susceptible tuberculosis (TB) patients may be low plasma levels of one or more of the first-line anti-TB drugs. The aim of this work was to develop an accurate and precise LC-MS/MS method for simultaneous quantification of all four first-line anti-TB drugs in plasma suitable for therapeutic drug monitoring (TDM). To adjust for degradation and losses during sample preparation, isotopically labeled compounds were used as internal standards. Plasma samples spiked with internal standards were extracted using protein precipitation with methanol and acetonitrile. Simultaneous separation of all four drugs was accomplished with a Chromolith Reversed-Phase column and mobile phases consisting of water, methanol, ammonium acetate and formic acid with subsequent mass spectrometric quantification. The linear range of the calibration curve for isoniazid was 0.5-10 mg/L, for rifampicin 0.75-30 mg/L, for ethambutol 0.25-10 mg/L and for pyrazinamide 4-80 mg/L. The lower limit of quantification was 0.5 mg/L, 0.75 mg/L, 0.25 mg/L and 4.0 mg/L, respectively. Precision estimated by the coefficient of variation was <15% for all four drugs. The LC-MS/MS method can readily be used for simultaneous quantification of first-line anti-TB drugs in plasma and is well suited for TDM.

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Section: Resultsmentioning

confidence: 99%

Simultaneous quantification of isoniazid, rifampicin, ethambutol and pyrazinamide by liquid chromatography/tandem mass spectrometry

Prahl

Lundqvist

Bahl

et al. 2016

APMIS

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“…MIC variability should ideally be taken into account to set clinically meaningful susceptibility breakpoints [125]. Several studies have been carried out in patients with pulmonary tuberculosis receiving the standard four-drug treatment, in which the plasma concentrations of these first-line anti-TB drugs were measured in an attempt to correlate them to therapeutic outcome [e.g., 55,56,61,[126][127][128][129]. A more comprehensive overview of these studies can be found in the review articles by Peloquin [8,123].…”

Section: Plasma Anti-tb Drug Concentrations and Tdmmentioning

confidence: 99%

Optimizing treatment outcome of first-line anti-tuberculosis drugs: the role of therapeutic drug monitoring

Verbeeck

Günther²,

Kibuule

et al. 2016

Eur J Clin Pharmacol

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“…Studies in patients with drug-susceptible tuberculosis (DS-TB) on a standard regimen of rifampin and isoniazid for 6 months with pyrazinamide and ethambutol for the first 2 months, suggest that such variability is clinically important. Specifically, patients with relatively low systemic exposures to rifampin and pyrazinamide have worse treatment outcomes [4,6], while rifampin, isoniazid and pyrazinamide exposures are related to the decline in bacterial load in the sputum during the weeks following initiation of treatment [6,8,[14][15][16][17][18]. For ethambutol and isoniazid, as well as second-line drugs for drug-resistant tuberculosis (DR-TB), such as linezolid, cycloserine, moxifloxacin, aminoglycosides, and capreomycin toxicity, are dose-related.…”

Section: Introductionmentioning

confidence: 99%

Current research toward optimizing dosing of first-line antituberculosis treatment

McIlleron

Chirehwa

2018

Expert Review of Anti-infective Therapy

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Introduction: Drug concentrations in tuberculosis patients on standard regimens vary widely with clinically important consequences.Areas covered: We review the available literature identifying factors correlated with pharmacokinetic variability of antituberculosis drugs. Based on population pharmacokinetic models and the weight, height, and sex distributions in a large data base of African tuberculosis patients, we propose simplified weight-based doses of the available fixed dose combination(FDC) for adults with drug susceptible tuberculosis. Emerging studies will support optimized weight-based dosing for children. Other sources of important pharmacokinetic variability include genetic variants, drug-drug interactions, formulation quality, and methods of preparation and administration.Expert commentary: Optimized weight band-based dosing will result in more equitable distribution of drug exposures by weight. The use of high doses of isoniazid in patients with drug-resistant tuberculosis would be safer and more effective if a feasible test was developed to allow stratified dosing according to acetylator type. There is an urgent need for more suitable formulations of many second-line drugs for children. The adoption of new technologies and efficient FDC design may allow further advances for patients and treatment programs. Lastly, current efforts to ensure adequate quality of antituberculosis drug products are not preventing the use of substandard products to treat patients with tuberculosis.

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Serum drug concentrations of INH and RMP predict 2-month sputum culture results in tuberculosis patients

Abstract: Among our study population, low SDCs of INH and, to a lesser extent, RMP, appear to be associated with reduced sputum culture conversion after 2 months of treatment.

Cited by 23 publications

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Simultaneous quantification of isoniazid, rifampicin, ethambutol and pyrazinamide by liquid chromatography/tandem mass spectrometry

Simultaneous quantification of isoniazid, rifampicin, ethambutol and pyrazinamide by liquid chromatography/tandem mass spectrometry

Optimizing treatment outcome of first-line anti-tuberculosis drugs: the role of therapeutic drug monitoring

Current research toward optimizing dosing of first-line antituberculosis treatment

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