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Drug Effect of Clof...
Drug Effect of Clofazimine on Persisters Explains an Unexpected Increase in Bacterial Load in Patients
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- Faraj, Alan (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri
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- Svensson, Robin J. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Diacon, Andreas H. (författare)
- TASK Appl Sci, Cape Town, South Africa.;Stellenbosch Univ, Div Physiol, Fac Med & Hlth Sci, Tygerberg, South Africa.
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- Simonsson, Ulrika S H, Professor (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri
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(creator_code:org_t)
- AMER SOC MICROBIOLOGY, 2020
- 2020
- Engelska.
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Ingår i: Antimicrobial Agents and Chemotherapy. - : AMER SOC MICROBIOLOGY. - 0066-4804 .- 1098-6596. ; 64:5
- Relaterad länk:
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Abstract
Ämnesord
Stäng
- Antituberculosis (anti-TB) drug development is dependent on informative trials to secure the development of new antibiotics and combination regimens. Clofazimine (CLO) and pyrazinamide (PZA) are important components of recommended standard multidrug treatments of TB. Paradoxically, in a phase IIa trial aiming to define the early bactericidal activity (EBA) of CLO and PZA monotherapy over the first 14 days of treatment, no significant drug effect was demonstrated for the two drugs using traditional statistical analysis. Using a model-based analysis, we characterized the statistically significant exposure-response relationships for both drugs that could explain the original findings of an increase in the numbers of CFU with CLO treatment and no effect with PZA. Sensitive analyses are crucial for exploring drug effects in early clinical trials to make the right decisions for advancement to further development. We propose that this quantitative semimechanistic approach provides a rational framework for analyzing phase IIa EBA studies and can accelerate anti-TB drug development.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- Mycobacterium tuberculosis
- drug development
- pharmacodynamics
- pharmacokinetics
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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