TY - JOUR
T1 - Pharmacokinetics of ethambutol under fasting conditions, with food, and with antacids
AU - Peloquin, Charles A.
AU - Bulpitt, Amy E.
AU - Jaresko, George S.
AU - Jelliffe, Roger W.
AU - Childs, James M.
AU - Nix, David E.
PY - 1999/3
Y1 - 1999/3
N2 - 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 for 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 μg/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-∞)) of 28.9 ± 4.7 μg · h/ml. In the presence of antacids, subjects had a mean C(max) of 3.3 ± 0.5 μg/ml, T(max) of 2.9 ± 1.2 h, and AUC(0-∞) of 27.5 ± 5.9 μg · 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 μg/ml, T(max) of 3.2 ± 1.3 h, and AUC(0- ∞) of 29.6 ± 4.7 μg · h/ml. These reductions in C(max), delays in T(max), and modest reductions in AUC(0-∞) can be avoided by giving EMB on an empty stomach whenever possible.
AB - 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 for 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 μg/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-∞)) of 28.9 ± 4.7 μg · h/ml. In the presence of antacids, subjects had a mean C(max) of 3.3 ± 0.5 μg/ml, T(max) of 2.9 ± 1.2 h, and AUC(0-∞) of 27.5 ± 5.9 μg · 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 μg/ml, T(max) of 3.2 ± 1.3 h, and AUC(0- ∞) of 29.6 ± 4.7 μg · h/ml. These reductions in C(max), delays in T(max), and modest reductions in AUC(0-∞) can be avoided by giving EMB on an empty stomach whenever possible.
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U2 - 10.1128/aac.43.3.568
DO - 10.1128/aac.43.3.568
M3 - Article
C2 - 10049268
AN - SCOPUS:0032982102
SN - 0066-4804
VL - 43
SP - 568
EP - 572
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 3
ER -