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Drug effect of clof...
Drug effect of clofazimine on persisters explain an unexpected increase in bacterial load from patients
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- Faraj, Alan (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri
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- Svensson, Robin J. (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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Diacon, Andreas H. (author)
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- Simonsson, Ulrika S H, Professor (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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(creator_code:org_t)
- English.
- Related links:
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https://urn.kb.se/re...
Abstract
Subject headings
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- Tuberculosis (TB) drug development is dependent on informative trials to secure development of new antibiotics and combination regimens. Clofazimine (CFZ) and pyrazinamid (PZA) are important components of recommended standard multi-drug treatments of TB. Paradoxically, in a Phase IIa trial aiming to define the early bactericidal activity (EBA) of CFZ 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 statistically significant exposure-response relationships for both drugs that could explain the original findings of increase in colony forming units (CFU) with CFZ treatment and no effect with PZA. Sensitive analyses are crucial for exploring drug effects in early clinical trials to make right decisions for advancement to further development. We propose that this quantitative semi-mechanistic approach provides a rational framework for analysing Phase IIa EBA studies, and can accelerate anti-TB drug development.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- Pharmacometrics
- Pharmacodynamics
- Pharmacokinetics
- Biomarker
- Tuberculosis
- Farmaceutisk vetenskap
- Pharmaceutical Science
Publication and Content Type
- vet (subject category)
- ovr (subject category)
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