The Relationship Between The Blood Concentration Of Isoniazid, Rifampicin, Pyrazinamide And The Treatment Outcomes Of Pulmonary Tuberculosis Patients
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Date
2017-04
Authors
Mahjoub, Abdallah Abdallah
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
A prospective cohort study was conducted in Hospital Pulau Pinang to find out the determinants of the pharmacokinetics of isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA), and to assess the effect of these pharmacokinetic parameters on the treatment outcomes of pulmonary tuberculosis patients. Plasma concentration of INH, RIF, and PZA was measured by new HPLC methods developed and validated as part of this study. The median of maximum plasma concentration (Cmax) of INH, RIF, and PZA was 4.75, 6.85, and 42.00 mg/L respectively. The median of the area under the time -concentration curve from zero to 24 hours (AUC0-24h) of INH and RIF was 20.1 and 33.2mg × h/ L respectively. The log INH Cmax, and log INH AUC0-24h were respectively significantly higher by 33%, (P = 0.000), and 25% (P = 0.000) in Indian patients. Log INH Cmax and log INH AUC0-24h were respectively reduced by 20% (P = 0.042), and by 23% (P = 0.000) in alcoholic patients. Respectively, the log RIF Cmax and the AUC0-24h of RIF were higher by 14% (P = 0.018), 23% (P = 0.026) in diabetic patients. RIF AUC0-24h was significantly lower in alcoholic patients by 27.6% (P = 0.042). Log PZA Cmax was significantly higher by 5% (P = 0.004), in Indian patients. At the end of intensive phase 84.7% of the initially smear positive patients were converted to smear negative status. The conversion of positive sputum smear was significant and positively affected by the baseline patients‟ body weight (adjusted OR = 1.24; 95% CI = 1.05 – 1.48, P = 0.011), the baseline total protein concentration (adjusted OR =
1.20; 95% CI = 1.02 – 1.41, P = 0.026), and negatively affected by tobacco smoking (adjusted OR = 39.8%; 95% CI = 1.55 – 1023.2, P = 0.026).
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Keywords
The relationship between the blood concentration of isoniazid , treatment outcomes of pulmonary tuberculosis patients