Pharmacokinetics of ethambutol in children and adults with tuberculosis
Abstract:SETTING: Five hospitals in the United States.
OBJECTIVE: To describe ethambutol pharmacokinetics in children and adults with active tuberculosis (TB).
DESIGN: Prospective, open-labeled study in 56 adults and 14 children with active tuberculosis who received ethambutol as part of their multidrug TB regimens.
RESULTS: Most serum samples were collected up to 10 h post dose and assayed using a validated gas chromatography assay with mass selective detection (GC/MS). Concentration data were analyzed using non-compartmental and population pharmacokinetic methods. Drug exposure increased with dose, but less than proportionally at doses >3000 mg. Lower than expected maximum serum concentrations (Cmax <2 μg/ml) were common in adults. Very low Cmax (<1 μg/ml) were common in children, as was delayed absorption (time to Cmax >3 h). Many Cmax were at or below typical TB minimal inhibitory concentrations. Cmax values for HIV-positive patients were 20% lower than HIV-negative patients with daily doses, but were similar with larger twice-weekly doses.
CONCLUSIONS: Adult TB patients often had lower than expected ethambutol serum concentrations, and most pediatric TB patients had very low ethambutol serum concentrations. Higher doses and therapeutic drug monitoring may be indicated for many of these patients.
Document Type: Regular Paper
Affiliations: 1: Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado, USA 2: Denver Public Health Department, Denver, Colorado, USA 3: Baylor College of Medicine, Houston, Texas, USA 4: AG Holly State Hospital, Lantana, Florida, USA 5: SUNY Children's Medical Center, Brooklyn, New York, USA 6: Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado, USA; and School of Pharmacy, University of Colorado, Denver, Colorado, USA 7: Laboratory of Applied Pharmacokinetics, University of Southern California, Los Angeles, California, USA; and School of Medicine, University of Southern California, Los Angeles, California, USA 8: Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado, USA; School of Pharmacy, University of Colorado, Denver, Colorado, USA; and School of Medicine, University of Colorado, Denver, Colorado, USA
Publication date: November 1, 2004
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