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Disposition kinetics of ethambutol in man

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Abstract

Six normal adult volunteers were administered 15 mg/kg of ethambutol (EMB) by a constant-rate 1-hr infusion. Plasma and urine samples were collected up to 24 and 72 hr, respectively. Peak plasma levels following the 1-hr infusion ranged from 11.6 to 15.4 μg/ml. Subsequent postinfusion EMB levels exhibited multiphasic decay. In the 12-hr period following infusion, EMB levels showed biexponential decay. However, 24-hr plasma levels in all subjects were observed to be higher than those predicted using a two-compartment body model. The α phase in these subjects had a mean half-life of 8.6 min while the half-life of the β phase ranged from 2.5 to 3.6 hr (mean 3.1). The half-life of the γ phase estimated from plasma data points between 12 and 24 hr averaged 11.2±3.6 hr. A terminal γt1/2 of 15.4±1.7 hr was calculated from 12–72 hr urine data. The mean value for the steady-state volume of distribution using a noncompartmental method was 3.89 liters/kg. Plasma EMB clearance ranged from 7.47 to 9.87 ml/min/kg (mean 8.57). The fraction of the dose eliminated unchanged varied from 0.75 to 0.84 (mean 0.79). Renal clearance ranged from 5.93 to 8.45 ml/min/kg (mean 6.81), indicating active tubular secretion.

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Author information

Author notes

  1. Ching S. Lee

    Present address: Department of Pharmaceutics, College of Pharmacy, University of Florida, 32610, Gainesville, Florida

  2. D. Craig Brater

    Present address: Departments of Pharmacology and Medicine, University of Texas Health Center, 75235, Dallas, Texas

Authors and Affiliations

  1. Department of Pharmacy, School of Pharmacy, University of California, 94143, San Francisco, California

    Ching S. Lee & Leslie Z. Benet

  2. Division of Clinical Pharmacology, Department of Medicine, University of California, San Francisco

    D. Craig Brater

  3. Division of Clinical Pharmacy, School of Pharmacy, University of California, 94143, San Francisco, California

    John G. Gambertoglio

Authors
  1. Ching S. Lee
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  2. D. Craig Brater
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  3. John G. Gambertoglio
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  4. Leslie Z. Benet
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Additional information

This work was supported in part by NIH Grant GM 26551.

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Lee, C.S., Brater, D.C., Gambertoglio, J.G. et al. Disposition kinetics of ethambutol in man. Journal of Pharmacokinetics and Biopharmaceutics 8, 335–346 (1980). https://doi.org/10.1007/BF01059382

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  • DOI: https://doi.org/10.1007/BF01059382

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