OBJECTIVES: Concomitant food intake influences pharmacokinetics of first-line anti- @entity1906 drugs in healthy volunteers. However, in treatment-naive @entity1906 @entity1 who are starting with drug treatment, data on the influence of food intake on the pharmacokinetics are absent. This study aimed to quantify the influence of food on the pharmacokinetics of @entity3109 , @entity1215 , @entity3110 and @entity5585 in @entity1906 patients starting anti- @entity1906 treatment. METHODS: A prospective randomized cross-over pharmacokinetic study was conducted in treatment-naive adults with drug-susceptible @entity1906 . They received @entity3109 , @entity1215 and @entity3110 intravenously and oral @entity5585 on day 1, followed by oral administration of these drugs under fasted and fed conditions on two consecutive days. Primary outcome was the bioavailability while fasting and with concomitant food intake. This study was registered with clinicaltrials.gov identifier NCT02121314. RESULTS: Twenty subjects completed the study protocol. Absolute bioavailability in the fasted state and the fed state was 93% and 78% for @entity3109 , 87% and 71% for @entity1215 and 87% and 82% for @entity3110 . Food decreased absolute bioavailability of @entity3109 and @entity1215 by 15% and 16%, respectively. @entity5585 AUC0-24 was comparable for the fasted state (481 mg  h/L) and the fed state (468 mg  h/L). Food lowered the maximum concentrations of @entity3109 , @entity1215 and @entity5585 by 42%, 22% and 10%, respectively. Time to maximum concentration was delayed for @entity3109 , @entity1215 and @entity5585 . The pharmacokinetics of @entity3110 were unaffected by food. CONCLUSIONS: Food decreased absolute bioavailability and maximum concentration of @entity3109 and @entity1215 , but not of @entity3110 or @entity5585 , in treatment-naive @entity1906 @entity1 . In @entity1 prone to low drug exposure, this may further compromise treatment efficacy and increase the risk of acquired drug resistance.

Impact of food on the pharmacokinetics of first-line anti- @entity1906 drugs in treatment-naive @entity1906 XXXX : a randomized cross-over trial.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity3110 :: ('MESH:D004977', 'Chemical') :: ['ethambutol'] @entity5585 :: ('MESH:D011718', 'Chemical') :: ['Pyrazinamide', 'pyrazinamide'] @entity3109 :: ('MESH:D007538', 'Chemical') :: ['isoniazid'] @entity1906 :: ('MESH:D014390', 'Disease') :: ['TB'] @entity1215 :: ('MESH:D012293', 'Chemical') :: ['rifampicin']
@entity1 :: (9606,Species) :: ['patients']
