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 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 (Cmax) of 4.5 +/- 1.0 micrograms/ml, time to maximum concentration of drug in serum (Tmax) of 2.5 +/- 0.9 h, and area under the concentration-time curve from 0 h to infinity (AUC0-infinity) of 28.9 +/- 4.7 micrograms.h/ml. In the presence of antacids, subjects had a mean Cmax of 3.3 +/- 0.5 micrograms/ml, Tmax of 2.9 +/- 1.2 h, and AUC0-infinity of 27.5 +/- 5.9 micrograms.h/ml. In the presence of the Food and Drug Administration high-fat meal, subjects had a mean Cmax of 3.8 +/- 0.8 micrograms/ml, Tmax of 3.2 +/- 1.3 h, and AUC0-infinity of 29.6 +/- 4.7 micrograms.h/ml. These reductions in Cmax, delays in Tmax, and modest reductions in AUC0-infinity can be avoided by giving EMB on an empty stomach whenever possible.
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA. peloquinc@njc.org
C A
CA
Peloquin
A E
AE
Bulpitt
G S
GS
Jaresko
R W
RW
Jelliffe
J M
JM
Childs
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DE
Nix
D000328:Adult; D000863:Antacids / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D004977:Ethambutol / Q000493:pharmacokinetics*; D005215:Fasting / Q000378:metabolism*; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008954:Models, Biological
D000863:Antacids; D000995:Antitubercular Agents; D004977:Ethambutol