Pharmacokinetics of ethambutol under fasting conditions, with food, and with antacids

Ethambutol (EMB) is the, most frequent "fourth drug" used for the empiric treatment of Mycobacterium tuberculosis and a frequently used. drug for infections caused by Mycobacterium avium complex, The pharmacokinetics of EMB in serum were studied with 14 healthy males and females in a randomized, four-period crossover study, Subjects ingested single, doses of EMB of 25 mg/kg of body weight under fasting conditions twice, with a high-fat meal, and with aluminum-magnesium antacid. Serum was collected fur 48 h and assayed by gas chromatography-mass spectrometry. Data were analyzed by noncompartmental methods and by a two-compartment pharmacokinetic model with zero-order absorption and first-order elimination, Both fasting conditions produced similar results: a mean (+/- standard deviation) EMB maximum concentration of drug in serum (C-max) of 4.5 +/- 1.0 mu g/ml, time to maximum concentration of drug in serum (T-max) of 2.5 +/- 0.9 h, and area under the concentration-time curve from 0 h to infinity (AUC(0-infinity)) of 28.9 +/- 4.7 mu g . h/ml. In the presence of antacids, subjects had a mean C-max of 3.3 +/- 0.5 mu g/ml, T-max of 2.9 +/- 1.2 h, and AUC(0-infinity) of 27.5 +/- 5.9 mu g . h/ml. In the presence of the. Food and Drug Administration high-fat meal, subjects had a mean C-max of 3.8 +/- 0.8 mu g/ml, T-max of 3.2 +/- 1.3 h, and AUC(0-infinity) of 29.6 +/- 4.7 mu g . h/ml. These reductions in C-max, delays in T-max, and modest reductions in AUC(0-infinity) can be avoided by giving EMB on an empty stomach whenever possible.