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Effect of Clofazimi...
Effect of Clofazimine Concentration on QT Prolongation in Patients Treated for Tuberculosis
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- Abdelwahab, Mahmoud Tareq (författare)
- Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa.
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- Court, Richard (författare)
- Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa.
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- Everitt, Daniel (författare)
- Global Alliance TB Drug Dev, New York, NY USA.
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- Diacon, Andreas H. (författare)
- Stellenbosch Univ, Dept Med, Tygerberg, South Africa.;Task Appl Sci, Bellville, South Africa.
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- Dawson, Rodney (författare)
- Univ Cape Town, Div Pulmonol, Lung Inst, Cape Town, South Africa.;Univ Cape Town, Dept Med, Lung Inst, Cape Town, South Africa.
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- Svensson, Elin, 1985- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Institutionen för farmaci,Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands.;Uppsala Univ, Dept Pharm, Uppsala, Sweden.
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- Maartens, Gary (författare)
- Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa.;Univ Cape Town, Wellcome Ctr Infect Dis Res Africa, Inst Infect Dis & Mol Med, Cape Town, South Africa.
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- Denti, Paolo (författare)
- Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa.
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Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa Global Alliance TB Drug Dev, New York, NY USA. (creator_code:org_t)
- American Society for Microbiology, 2021
- 2021
- Engelska.
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 65:7
- Relaterad länk:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Clofazimine is classified as a WHO group B drug for the treatment of rifampin-resistant tuberculosis. QT prolongation, which is associated with fatal cardiac arrhythmias, is caused by several antitubercular drugs, including clofazimine, but there are no data quantifying the effect of clofazimine concentration on QT prolongation. Our objective was to describe the effect of clofazimine exposure on QT prolongation. Fifteen adults drug-susceptible tuberculosis patients received clofazimine monotherapy as 300mg daily for 3 days, followed by 100mg daily in one arm of a 2-week, multiarm early bactericidal activity trial in South Africa. Pretreatment Fridericia-corrected QT (QTcF) (105 patients, 524 electrocardiograms [ECGs]) and QTcFs from the clofazimine monotherapy arm matched with clofazimine plasma concentrations (199 ECGs) were interpreted with a nonlinear mixed-effects model. Clofazimine was associated with significant QT prolongation described by a maximum effect (Emax) function. We predicted clofazimine exposures using 100-mg daily doses and 2 weeks of loading with 200 and 300mg daily, respectively. The expected proportions of patients with QTcF change from baseline above 30 ms (DQTcF. 30) were 2.52%, 11.6%, and 23.0% for 100-, 200-, and 300-mg daily doses, respectively. At steady state, the expected proportion with Delta QTcF of >30 ms was 23.7% and with absolute QTcF of >450 ms was 3.42% for all simulated regimens. The use of loading doses of 200 and 300mg is not predicted to expose patients to an increased risk of QT prolongation, compared with the current standard treatment, and is, therefore, an alternative option for more quickly achieving therapeutic concentrations.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- Monte Carlo simulation
- multidrug resistance
- pharmacodynamics
- population pharmacokinetics
- tuberculosis
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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