Effect of diabetes mellitus on TB drug concentrations in Tanzanian patients.

Autor:	Mtabho CM; Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre, Moshi, Tanzania., Semvua HH; Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre, Moshi, Tanzania., van den Boogaard J; Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre, Moshi, Tanzania.; Radboud university medical center, Department of Lung Diseases & Radboud Institute for Health Sciences, Nijmegen, The Netherlands., Irongo CF; Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre, Moshi, Tanzania.; National Tuberculosis and Leprosy Programme, Kilimanjaro Region, Tanzania., Boeree MJ; Radboud university medical center, Department of Lung Diseases & Radboud Institute for Health Sciences, Nijmegen, The Netherlands., Colbers A; Radboud university medical center, Department of Pharmacy & Radboud Institute for Health Sciences, Nijmegen, The Netherlands., Burger DM; Radboud university medical center, Department of Pharmacy & Radboud Institute for Health Sciences, Nijmegen, The Netherlands., van Crevel R; Radboud university medical center, Department of Internal Medicine & Radboud Institute for Health Sciences, Nijmegen, The Netherlands., van der Ven AJAM; Radboud university medical center, Department of Internal Medicine & Radboud Institute for Health Sciences, Nijmegen, The Netherlands., Kibiki GS; Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre, Moshi, Tanzania., Tostmann A; Radboud university medical center, Department of Lung Diseases & Radboud Institute for Health Sciences, Nijmegen, The Netherlands., Aarnoutse RE; Radboud university medical center, Department of Pharmacy & Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
Jazyk:	angličtina
Zdroj:	The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2019 Dec 01; Vol. 74 (12), pp. 3537-3545.
DOI:	10.1093/jac/dkz368
Abstrakt:	Background: Diabetes mellitus (DM) is associated with poor TB treatment outcome. Previous studies examining the effect of DM on TB drug concentrations yielded conflicting results. No studies have been conducted to date in an African population. Objectives: To compare exposure to TB drugs in Tanzanian TB patients with and without DM. Patients and Methods: A prospective pharmacokinetic study was performed among 20 diabetic and 20 non-diabetic Tanzanian TB patients during the intensive phase of TB treatment. Plasma pharmacokinetic parameters of isoniazid, rifampicin, pyrazinamide and ethambutol were compared using an independent-sample t-test on log-transformed data. Multiple linear regression analysis was performed to assess the effects of DM, gender, age, weight, HIV status and acetylator status on exposure to TB drugs. Results: A trend was shown for 25% lower total exposure (AUC0-24) to rifampicin among diabetics versus non-diabetics (29.9 versus 39.9 mg·h/L, P=0.052). The AUC0-24 and peak concentration (Cmax) of isoniazid were also lower in diabetic TB patients (5.4 versus 10.6 mg·h/L, P=0.015 and 1.6 versus 2.8 mg/L, P=0.013). Pyrazinamide AUC0-24 and Cmax values were non-significantly lower among diabetics (P=0.08 and 0.09). In multivariate analyses, DM remained an independent predictor of exposure to isoniazid and rifampicin, next to acetylator status for isoniazid. Conclusions: There is a need for individualized dosing of isoniazid and rifampicin based on plasma concentration measurements (therapeutic drug monitoring) and for clinical trials on higher doses of these TB drugs in patients with TB and DM. (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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