Serum Concentrations of Antimycobacterial Drugs in Patients with Pulmonary Tuberculosis in Botswana

Tappero, Jordan W.; Bradford, Williamson Z.; Agerton, Tracy B.; Hopewell, Philip C.; Reingold, Arthur; Lockman, Shahin; Oyewo, Aderonke; Talbot, Elizabeth A.; Kenyon, Thomas; Moeti, Themba; Moffat, Howard; Peloquin, Charles A.

doi:10.1086/431984

Cited by 132 publications

(111 citation statements)

References 28 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is severalfold lower than the estimated levels required for optimal efficacy (11). Furthermore, in keeping with the findings of several other studies with tuberculosis patients (4,7,20,26,28), low peak concentrations in comparison to the published reference range (18) were demonstrated in the majority of patients. Autoinduction of rifampin's metabolism is expected to result in lower levels after repeated doses (9,24), and this might explain in part the relatively low concentrations in the patient studies.…”

Section: Discussionsupporting

confidence: 85%

Determinants of Rifampin, Isoniazid, Pyrazinamide, and Ethambutol Pharmacokinetics in a Cohort of Tuberculosis Patients

McIlleron

Wash

Burger

et al. 2006

Antimicrob Agents Chemother

228

219

View full text Add to dashboard Cite

Evaluation of sources of pharmacokinetic variation can facilitate optimization of tuberculosis treatment regimens by identification of avoidable sources of variation and of risk factors for low or high drug concentrations in patients. Our objective was to describe the pharmacokinetics of rifampin, isoniazid, pyrazinamide, and ethambutol in a cohort of tuberculosis patients established on first-line treatment regimens and to evaluate the determinants of pharmacokinetic variation. Plasma concentration-time profiles were determined for each of the drugs in 142 patients with drug-sensitive pulmonary tuberculosis after 2 months of daily treatment in hospital. Pharmacokinetic measures were described by noncompartmental analysis. Multiple linear regression was used to evaluate the patient and the treatment factors associated with variation of the area under the concentration-time curve from 0 to 8 h. Several factors independently associated with variations in antituberculosis drug concentrations were identified: human immunodeficiency virus infection was associated with 39% and 27% reductions for rifampin and ethambutol, respectively; formulation factors were determinants of rifampin and isoniazid bioavailability; female patients had increased rifampin and isoniazid concentrations but reduced ethambutol concentrations; older patients had higher levels of isoniazid and ethambutol; patients with a history of previous antituberculosis treatment had lower ethambutol concentrations; and the dose per kilogram of body weight was associated with the concentrations of all four agents. Further studies are required to assess the implications of variations in antituberculosis drug concentrations for efficacy and safety before decisions are made to change the dosing strategy in patients at risk.

show abstract

Section: Discussionsupporting

confidence: 85%

Determinants of Rifampin, Isoniazid, Pyrazinamide, and Ethambutol Pharmacokinetics in a Cohort of Tuberculosis Patients

McIlleron

Wash

Burger

et al. 2006

Antimicrob Agents Chemother

228

219

View full text Add to dashboard Cite

show abstract

“…In particular, CSF penetration of rifampicin, the key drug in TBM treatment, is poor, as is that of ethambutol and streptomycin [75][76][77]. Isoniazid and pyrazinamide penetrate more readily [78,79].…”

Section: Specific Antituberculous Treatmentmentioning

confidence: 99%

Tuberculous Meningitis in Adults: A Review of a Decade of Developments Focusing on Prognostic Factors for Outcome

2012

View full text Add to dashboard Cite

Tuberculous meningitis (TBM) is the most severe form of TB. Despite treatment, mortality and long-term disability remain unacceptably high. Prevention, early recognition, diagnosis and treatment are fundamental to improving outcomes. However, an effective vaccine remains elusive, initial symptoms are nonspecific, and sensitive diagnostic tests are not available. There has been progress in our understanding of the immunopathology of TBM, and several factors have been found to be associated with susceptibility to infection, disease progression and clinical outcome. However, these have not yet impacted on treatment. Early treatment initiation and uninterrupted continuation, severity on presentation, seizures, stroke, cranial nerve involvement, cerebrospinal fluid cell count and lactate levels, hyponatreamia and coinfection with HIV are all found to be important prognostic factors for outcome. Pathogen lineage (Beijing genotype) and host genetics (polymorphisms in TLR2, TIRAP and LTA4H genes) can influence susceptibility to TBM. However, these findings have not yet impacted on treatment. Progress in vaccine development, opportunities for better diagnostic tests, novel insights into pathogenesis and an increasing evidence base for improving treatment should impact the current high mortality and morbidity, if translated to global and local guidelines.

show abstract

“…The cell wall allows the bacteria to survive within macrophages because it has high lipid content (Katzung, 2011), (Williams and Lemake, 2002). Poor health due to malnutrition is observed in most TB patients, compared with the controls previously (Tappero, et al, 2005), (Tsukaguchi, et al, 1991). The disease-induced production of certain cytokines such as interleukin-6 and tumor necrosis factorproduced during tuberculosis may induce fever, hepatic synthesis of acute phase reactant proteins, inhibit production of serum albumin and plasma concentrations of some important micronutrients are changed dramatically (Beisel, 1998).…”

mentioning

confidence: 91%

Untitled

2017

RJLBPCS

View full text Add to dashboard Cite

ABSTRACT:Mycobacterium tuberculosis infection on the biochemical and demographic parameters of the TB patients were compared with that of the healthy population of local population.Blood samples were collected from healthy and TB patients at chest ward DHQ Hospital Faisalabad after taking informed consent from patients. The study was ethically approved by graduate / ethical committee. Demographic data and biochemical parameters were determined in all patients and healthy volunteers. Results were compared at 95% confidence interval. The patients with pulmonary tuberculosis triggered decreased BMI and low concentration of glucose, total cholesterol, albumin and globulin while higher concentrations of creatinine and an increased activity of alkaline phosphatase, SGPT and SGOT in blood. There seen a number of parameters that differs in diseased patients compared to normal individuals that results in poor health status. Because of less availability of oxygen to the patients in the presence of oxygen competitor Mycobacterium Tuberculosis, creation of anaerobic environment may increase concentration of creatinine in the blood of patients.

show abstract

Serum Concentrations of Antimycobacterial Drugs in Patients with Pulmonary Tuberculosis in Botswana

Cited by 132 publications

References 28 publications

Determinants of Rifampin, Isoniazid, Pyrazinamide, and Ethambutol Pharmacokinetics in a Cohort of Tuberculosis Patients

Determinants of Rifampin, Isoniazid, Pyrazinamide, and Ethambutol Pharmacokinetics in a Cohort of Tuberculosis Patients

Tuberculous Meningitis in Adults: A Review of a Decade of Developments Focusing on Prognostic Factors for Outcome

Untitled

Contact Info

Product

Resources

About