Effect of diabetes mellitus on TB drug concentrations in Tanzanian patients.
J Antimicrob Chemother
; 74(12): 3537-3545, 2019 12 01.
Article
en En
| MEDLINE
| ID: mdl-31651031
ABSTRACT
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 ANDMETHODS:
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tuberculosis Pulmonar
/
Complicaciones de la Diabetes
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Diabetes Mellitus
/
Antituberculosos
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
País/Región como asunto:
Africa
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2019
Tipo del documento:
Article
País de afiliación:
Tanzania