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Open Access Effect of tablet crushing on drug exposure in the treatment of multidrug-resistant tuberculosis

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SETTING: Treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) are poor. Due to drug toxicity and a long treatment duration, approximately half of patients are treated successfully. Medication is often crushed for patients who have difficulty swallowing whole tablets. Whether crushing tablets affects drug exposure in MDR-TB treatment is not known.

OBJECTIVE AND DESIGN: We performed a sequential pharmacokinetic study in patients aged >18 years on MDR-TB treatment at two hospitals in Cape Town, South Africa. We compared the bioavailability of pyrazinamide, moxifloxacin, isoniazid (INH), ethambutol and terizidone when the tablets were crushed and mixed with water before administration vs. swallowed whole. We sampled blood at six time points over 10 h under each condition separated by 2 weeks. Non-compartmental analysis was used to derive the key pharmacokinetic measurements.

RESULTS: Twenty participants completed the study: 15 were men, and the median age was 31.5 years. There was a 42% reduction in the area under the curve AUC0–10 of INH when the tablets were crushed compared with whole tablets (geometric mean ratio 58%; 90%CI 47–73). Crushing tablets of pyrazinamide, moxifloxacin, ethambutol and terizidone did not affect the bioavailability significantly.

CONCLUSION: We recommend that crushing of INH tablets in the MDR-TB treatment regimen be avoided. Paediatric INH formulations may be a viable alternative if the crushing of INH tablets is indicated.
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Keywords: MDR-TB; bioavailability; bioequivalence; crushed; pharmacokinetic

Document Type: Research Article

Affiliations: 1: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town 2: Brooklyn Chest Hospital, Cape Town 3: DP Marais Hospital, Cape Town, South Africa 4: Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA

Publication date: October 1, 2019

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on lung health world-wide.

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