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Evidence of nonlinearity in digoxin pharmacokinetics

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Abstract

Six normal male volunteers received 0.5 mg label doses of digoxin as (a) a bolus intravenous injection over 2 min, (b) a constant rate intravenous infusion over 1 hr, (c) a constant rate intravenous infusion over 3 hr, and (d) a solution in 5% dextrose given orally. Plasma concentrations of digoxin were measured by radioimmunoassay for a 4 day period and urinary excretion for a 6 day period after the single doses. The mean (coefficient of variation) total areas under the plasma concentration-time curves per 0.5 mg of digoxin were (a) 35.55 (14.8%), (b) 30.20 (27.7%), (c) 25.80 (35.5%), and (d) 15.47 (49.9%); the means differed significantly (0.01>p>0.005). The mean (coefficient of variation) total amounts excreted in the urine as a fraction of the dose were (a) 0.689 (6.31%), (b) 0.517 (20.4%), (c) 0.588 (16.8%), and (d) 0.374 (23.4%); the means differed significantly (p<0.001. Both the total clearance and the nonrenal clearance of digoxin differed significantly with the method of intravenous administration. The slower the rate of input of digoxin to the body, the greater were both the total clearance and the nonrenal clearance of the drug, which strongly suggests nonlinear pharmacokinetics.

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Authors and Affiliations

  1. College of Pharmacy and Upjohn Center for Clinical Pharmacology, The University of Michigan Medical Center, 48109, Ann Arbor, Michigan

    J. G. Wagner & E. Sakmar

  2. Department of Internal Medicine (Cardiology), The University of Michigan Medical Center, 48109, Ann Arbor, Michigan

    K. D. Popat & S. K. Das

  3. Department of Pharmacology and Upjohn Center for Clinical Pharmacology, The University of Michigan Medical Center, 48109, Ann Arbor, Michigan

    H. Movahhed

Authors
  1. J. G. Wagner
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  2. K. D. Popat
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  3. S. K. Das
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  4. E. Sakmar
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  5. H. Movahhed
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Additional information

This work was supported in part by National Institutes of Health Grant 1 R01 HL 23862-01 and in part by National Institutes of Health General Clinical Research Center Grant 5M01 RR421.

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Wagner, J.G., Popat, K.D., Das, S.K. et al. Evidence of nonlinearity in digoxin pharmacokinetics. Journal of Pharmacokinetics and Biopharmaceutics 9, 147–166 (1981). https://doi.org/10.1007/BF01068079

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  • DOI: https://doi.org/10.1007/BF01068079

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