Pharmacokinetics of ethionamide administered under fasting conditions or with orange juice, food, or antacids

This study was conducted in order to (i) determine the effect of food, oran ge juice, or antacids on the absorption of a single oral 500-mg dose of eth ionamide (ETA) in healthy volunteers, including an assessment of bioequival ence, and (ii) determine ETA population pharmacokinetic (PK) parameters. Th e pharmacokinetics of ETA in serum was determined for 12 healthy males and females in a randomized, four-period crossover study, Volunteers received s ingle 500-mg doses of ETA either on an empty stomach (reference) or with fo od, orange juice, or antacids, Serum samples were collected for 48 h and as sayed by high-performance Liquid chromatography. Data were analyzed by nonc ompartmental and population methods. Mean test/reference ratios and 90% con fidence intervals were determined. No statistically significant differences were seen in the maximum concentration of ETA (C-max), time to maximum con centration (T-max), or area under the concentration-time curve from 0 h to infinity (AUC(0-infinity)) between the four treatments (P > 0.05 by analysi s of variance). The least-squares mean ratios (with confidence intervals in parentheses) for C-max were 105% (81.2 to 135%) after orange juice, 94% (7 2.8 to 121%) after food, and 88% (68.4 to 114%) after antacids, The least-s quares mean ratios (with confidence intervals is in parentheses) for AUG(0- infinity) were 91% (72.7 to 115%) after orange juice, 96% (76.4 to 121%) af ter food, and 95% (75.5 to 120%) after antacids. The mean T-max was slightl y prolonged following antacid or food administration (2.3 to 2.6 h) compare d to administration on an empty stomach or with juice (1.7 to 1.9 h), The m edian population PK parameters were as follows: K-a = 0.37 to 0.48 h(-1), V /F = 2.0 to 2.8 liters/kg, CL/F = 56.5 to 72.2 liters/h, and terminal half- life = 1.7 to 2.1 h, where K-a, is the absorption rate constant, V is the v olume of distribution, and CL is clearance, The PK behavior of ETA was not significantly modified by the different conditions studied. Mean ratios for AUC ranged from 0.91 to 0.96 for the orange juice, food, and antacid treat ments, indicating a minimal effect on relative bioavailability, ETA can, th erefore, be administered with food if tolerance is an issue.