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Van Der Walt Bj - One of the best experts on this subject based on the ideXlab platform.
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population screening for Isoniazid acetylator phenotype
Pharmacoepidemiology and Drug Safety, 2001Co-Authors: H I Seifart, D P Parkin, F J H Botha, P R Donald, Van Der Walt BjAbstract:Purpose To establish a useful method for acetylator phenotypification and therapeutic drug monitoring of patients receiving Isoniazid. Methods Sixty patients with uncomplicated pulmonary tuberculosis were given a 5-mg/kg oral dose of Isoniazid each. Plasma concentrations of Isoniazid and its metabolite, acetyl-Isoniazid, were determined by HPLC analyses at various post-dose times. From the Isoniazid concentration and the concentration ratio of acetyl-Isoniazid and Isoniazid (metabolic ratio), phenotypification methods were assessed. Results The metabolic ratios at 3 h post-dose revealed a trimodal distribution; a fast, intermediate and slow acetylator phenotype group. The 2-h and 6-h data showed different bimodal combinations of these phenotype groups. The metabolic ratio phenotypification method could be simplified by using the HPLC data directly without converting it to absolute concentrations. Conclusions A single-sample test based upon the plasma Isoniazid concentration, combined with the metabolic ratio of acetyl-Isoniazid and Isoniazid, appears to be a reliable parameter for phenotype discrimination and for bioavailability testing. Copyright © 2001 John Wiley & Sons, Ltd.
Alison H. Hammond - One of the best experts on this subject based on the ideXlab platform.
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Involvement of cytochrome P4502E1 in the toxicity of dichloropropanol to rat hepatocyte cultures
Toxicology, 1997Co-Authors: Alison H. HammondAbstract:Hepatocytes were isolated and cultured from untreated rats and rats treated with Isoniazid to induce cytochrome P4502E1. Isoniazid selectively increased p-nitrophenol hydroxylase activity in 2-h cultures, and increased the toxicity of both 1,3- and 2,3-dichloropropanol. Isoniazid also increased the rate and extent of glutathione depletion by the dichloropropanols. There was no effect of Isoniazid on the toxicity of 1,3-dichloroacetone, precocene II or allyl alcohol. In addition, diethyldithiocarbamate selectively inhibited p-nitrophenol hydroxylase in 2-h cultures from untreated and Isoniazid-treated rats, as well as abolishing toxicity of the dichloropropanols. In 24-h cultures from Isoniazid-treated rats diethyldithiocarbamate inhibited high affinity MCOD activity by 55% and there was also a small but significant inhibition of precocene II toxicity. These results indicate that Isoniazid-inducible P4502E1 can mediate the toxicity of dichloropropanol.
H I Seifart - One of the best experts on this subject based on the ideXlab platform.
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population screening for Isoniazid acetylator phenotype
Pharmacoepidemiology and Drug Safety, 2001Co-Authors: H I Seifart, D P Parkin, F J H Botha, P R Donald, Van Der Walt BjAbstract:Purpose To establish a useful method for acetylator phenotypification and therapeutic drug monitoring of patients receiving Isoniazid. Methods Sixty patients with uncomplicated pulmonary tuberculosis were given a 5-mg/kg oral dose of Isoniazid each. Plasma concentrations of Isoniazid and its metabolite, acetyl-Isoniazid, were determined by HPLC analyses at various post-dose times. From the Isoniazid concentration and the concentration ratio of acetyl-Isoniazid and Isoniazid (metabolic ratio), phenotypification methods were assessed. Results The metabolic ratios at 3 h post-dose revealed a trimodal distribution; a fast, intermediate and slow acetylator phenotype group. The 2-h and 6-h data showed different bimodal combinations of these phenotype groups. The metabolic ratio phenotypification method could be simplified by using the HPLC data directly without converting it to absolute concentrations. Conclusions A single-sample test based upon the plasma Isoniazid concentration, combined with the metabolic ratio of acetyl-Isoniazid and Isoniazid, appears to be a reliable parameter for phenotype discrimination and for bioavailability testing. Copyright © 2001 John Wiley & Sons, Ltd.
Maria N Tsolia - One of the best experts on this subject based on the ideXlab platform.
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the effectiveness of a 9 month regimen of Isoniazid alone versus 3 and 4 month regimens of Isoniazid plus rifampin for treatment of latent tuberculosis infection in children results of an 11 year randomized study
Clinical Infectious Diseases, 2007Co-Authors: Nikos P Spyridis, Panayotis Spyridis, Anna Gelesme, Vana Sypsa, Mina Valianatou, Flora Metsou, Dimitris Gourgiotis, Maria N TsoliaAbstract:Background. A 9-month course of Isoniazid monotherapy is currently recommended for the treatment of latent tuberculosis infection (LTBI) and has been shown to be effective in both children and adults. Reduced compliance with this regimen has forced physicians to explore shorter regimens. The aim of this study was to compare 3- and 4-month combination regimens of Isoniazid plus rifampin with a 9-month regimen of Isoniazid monotherapy for the treatment of LTBI in children. Methods. This prospective, randomized, controlled study was conducted over an 11-year period (1995-2005). In period 1 (1995-1998), 232 patients received Isoniazid therapy for 9 months (group A), and 238 patients received Isoniazid and rifampin for 4 months (group B). In period 2 (1999-2002), 236 patients were treated with Isoniazid and rifampin for 4 months (group C), and 220 patients received the same regimen for 3 months (group D). All patients were observed for ≥3 years. Results. Overall compliance with treatment was good, but patients who received Isoniazid monotherapy were less compliant than were those who received short-course combination therapy (P =.011, for group A vs. group B; P =.510, for group C vs. group D). No patient in any group developed clinical disease during the follow-up period. New radiographic findings suggestive of possible active disease were more common in patients who received Isoniazid monotherapy (24%) than in those treated with shorter regimens (11.8%, 13.6%, and 11% for groups B, C, and D, respectively; P =.001 for group A vs. group B; P =.418 for group C vs. group D). Serious drug-related adverse effects were not detected. Conclusions. Short-course treatment with Isoniazid and rifampin for 3-4 months is safe and seems to be superior to a 9-month course of Isoniazid monotherapy.
Tumaini J Nagu - One of the best experts on this subject based on the ideXlab platform.
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effects of Isoniazid resistance on tb treatment outcomes under programmatic conditions in a high tb and hiv setting a prospective multicentre study
Journal of Antimicrobial Chemotherapy, 2016Co-Authors: Tumaini J Nagu, Said Aboud, Mecky I Matee, Markus Maeurer, Wafaie W Fawzi, Ferdinand MugusiAbstract:Objectives The scale and impact of background Isoniazid resistance in TB- and HIV-endemic countries requires definition to improve treatment success and guide the scale-up of Isoniazid preventive therapy (IPT). We describe the effects of Isoniazid resistance on TB treatment outcomes among patients with or without HIV infection in Dar es Salaam, Tanzania. Methods A multicentre, prospective observational study was conducted among TB patients commencing WHO-recommended first-line TB treatment. In multivariate analysis we ascertained the relationship between Isoniazid resistance at presentation with a composite of poor treatment outcomes (death, failure or default from TB therapy). Results Of 861 patients, 250 (29.0%) were HIV infected and 23 (2.7%) had Isoniazid resistance. Seven hundred and ninety-seven (92.6%) of the patients were successfully treated and 25 (2.9%) died. Isoniazid resistance [relative risk (RR) = 6.0; 95% CI = 1.9-18.7; P < 0.01] and HIV infection with (RR = 2.3; 95% CI = 1.0-5.2; P = 0.05) or without (RR = 3.1; 95% CI = 1.5-6.2; P < 0.01) ART were independent predictors of poor treatment outcomes. Conclusions Background Isoniazid resistance and HIV infection adversely affected TB treatment outcomes. Early laboratory detection of Isoniazid resistance is important for successful TB therapy. Studies on the impact of background Isoniazid resistance on the efficacy of Isoniazid prophylaxis are recommended.
