Cure of tuberculosis despite serum concentrations of antituberculosis drugs below published reference ranges

Meloni, Monica, Corti, Natascia, Müller, Daniel, Henning, Lars, Gutteck, Ursula, von Braun, Amrei, Weber, Rainer, and Fehr, Jan (2015) Cure of tuberculosis despite serum concentrations of antituberculosis drugs below published reference ranges. Swiss Medical Weekly, 23 (145). w14223. pp. 1-10.

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Principles: Therapeutic target serum concentrations of first-line antituberculosis drugs have not been well defined in clinical studies in tuberculosis (TB) patients.

Methods: We retrospectively investigated the estimated maximum serum concentrations (eC max) of antituberculosis drugs and clinical outcome of TB patients with therapeutic drug monitoring performed between 2010-2012 at our institution, and follow-up until March 2014. The eC max was defined as the highest serum concentration during a sampling period (2, 4 and 6 hours after drug ingestion). We compared the results with published eC max values, and categorised them as either "within reference range", "low eC max", or "very low eC max".Low/very low eC max-levels were defined as follows: isoniazid 2-3/<2 mg/l, rifampicin 4-8/<4 mg/l, rifabutin 0.2-0.3/<0.2 mg/l, ethambutol 1-2/<0.1 mg/l and pyrazinamide <20 mg/l.

Results: Concentrations of antituberculosis drugs in 175 serum samples of 17 patients with TB were analysed. In 12 (71%) patients, multiple therapeutic drug monitoring samples were collected over time, in 5 (29%) patients only one sample was available for therapeutic drug monitoring. Overall, 94% of all patients had at least one low antituberculosis drug concentration. Overall, 64% of all eC max levels were classified as "low" or "very low". The eC max was below the relevant reference range in 80% of isoniazid, 95% of rifampicin, 30% of pyrazinamide, and 30% of ethambutol measurements. All but one patient were cured of tuberculosis.

Conclusions: Although many antituberculosis drug serum concentrations were below the widely used reference ranges, 16 of 17 patients were cured of tuberculosis. These results challenge the use of the published reference ranges for therapeutic drug monitoring.

Item ID: 49856
Item Type: Article (Research - C1)
ISSN: 1424-3997
Keywords: tuberculosis; antituberculosis drugs; therapeutic drug monitoring
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Funders: Gilead Sciences, Merck Sharp & Dome, Janssen, Bristol-Myers Squibb, Roche, ViiV, Abbvie, Boehringer Ingelheim, Novartism, Abbott, GlaxoSmithKline, Pfizer, Chemedica, Tibotec
Date Deposited: 14 Aug 2017 23:34
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111717 Primary Health Care @ 100%
SEO Codes: 92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920499 Public Health (excl. Specific Population Health) not elsewhere classified @ 100%
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