te Brake L. H. M., Ruslami R., Later-Nijland H., Mooren F., Teulen M., Apriani L., Koenderink J. B., Russel F. G., Burger D. M., Alisjahbana B., Wieringa Franck, van Crevel R., Aarnoutse R. E. (2015). Exposure to total and protein-unbound rifampin is not affected by malnutrition in indonesian tuberculosis patients. Antimicrobial Agents and Chemotherapy, 59 (6), p. 3233-3239. ISSN 0066-4804.
Titre du document
Exposure to total and protein-unbound rifampin is not affected by malnutrition in indonesian tuberculosis patients
Année de publication
2015
Auteurs
te Brake L. H. M., Ruslami R., Later-Nijland H., Mooren F., Teulen M., Apriani L., Koenderink J. B., Russel F. G., Burger D. M., Alisjahbana B., Wieringa Franck, van Crevel R., Aarnoutse R. E.
Source
Antimicrobial Agents and Chemotherapy, 2015,
59 (6), p. 3233-3239 ISSN 0066-4804
Nutritional status may have a profound impact on the pharmacokinetics of drugs, yet only few data are available for tuberculosis (TB) drugs. As malnutrition occurs frequently among TB patients, we assessed the effect of malnutrition on the steady-state pharmacokinetics of total and protein-unbound rifampin during the intensive phase of TB treatment. In a descriptive pharmacokinetic study in Bandung, Indonesia, patients received a fixed standard rifampin dose of 450 mg once daily during the intensive phase of TB treatment. A full pharmacokinetic curve for rifampin was recorded, and total and unbound concentrations of rifampin were analyzed in all samples. Rifampin pharmacokinetic parameters were compared between severely malnourished (BMI of <16.0 kg/m(2)), malnourished (BMI of <18.5 kg/m(2)), and well-nourished (BMI of >= 18.5 kg/m(2)) individuals. No difference in total and protein-unbound pharmacokinetic parameters between severely malnourished (n = 7), malnourished (n = 11), and well-nourished (n = 25) patients could be demonstrated. In addition, no significant correlation between BMI and exposure (area under the concentration-time curve from 0 to 24 h [ AUC(0-24)] and maximum concentration of drug in serum [C-max]) was found. Females had significantly higher total AUC(0-24) (geometric mean, 59.2 versus 48.2 h.mg/liter; P = 0.02) and higher unbound AUC(0-24) (geometric mean, 6.2 versus 4.8 h.mg/liter; P = 0.02) than males. Overall, a marked 2-fold interindividual variation in the free fraction was observed (7.6 to 15.0%; n = 36). Nutritional status and BMI do not appear to have a major effect on total and protein-unbound pharmacokinetic parameters of rifampin in Indonesian subjects. The large interindividual variability in the free fraction of rifampin suggests that protein-unbound rather than total rifampin concentrations should preferably be used to study exposure-response relationships.
Plan de classement
Santé : généralités [050]
;
Nutrition, alimentation [054]
Description Géographique
INDONESIE
Localisation
Fonds IRD [F B010065227]
Identifiant IRD
fdi:010065227
