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

Charles A. Peloquin, Amy E. Bulpitt, George S. Jaresko, Roger W. Jelliffe, James M. Childs, David E. Nix

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)568-572
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume43
Issue number3
DOIs
StatePublished - Mar 1999

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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