Impact of food intake on pharmacokinetics(PK) of first-line tuberculosis drugs in treatment-naive patients

Background: In treatment naive TB patients, the impact of food intake on the PK data of 1st line TB drugs is unknown in the early phase of treatment. Objectives: To assess impact of food intake on PK of isoniazid(INH), Rifampisin(RIF),pyrazinamide(PZA)and ethambutol(EMB) in treatment-naive TB patients. Methods: Randomized, cross-over trial in 20 patients. Subjects were administered INH, RIF, and EMB iv and PZA orally on day 1,and Fixed Drug Combination of all four on day 2&3 either while fasting or along with a high carbohydrate meal. Full PK curves were collected, and assayed by Liquid Chromatography-tandem Mass Spectrometry. Results: mean age was 41.8(SD=20)yrs, mean body mass index 17.48(SD=2.6)kg/m2. The PK data was shown in Conclusions: In treatment naive TB patients, concomitant food intake substantially influenced PK of TB drugs. Area under the curve(AUC0-24,),maximum concentration(Cmax ) and bioavailability decreased significantly when drugs were taken with food. The impact of the differences found in drug exposure on treatment efficacy and tolerability should be evaluated in a randomized prospective study. (Table Presented)