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Pharmacokinetics of digoxin: Relationship between response intensity and predicted compartmental drug levels in man

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Abstract

A study designed to investigate the relationship between the pharmacokinetics of digoxin and a measure of its pharmacological effect has been conducted. Serum digoxin concentrations and systolic time intervals were measured concurrently in 12 normal male volunteers following a 1.0 mg i.v. bolus injection. The averaged serum digoxin concentration- time and response-time data were analyzed pharmacokinetically using a three-compartment open model and nonlinear least- squares fitting. When only the serum level-time data were analyzed, a close relationship was found between calculated digoxin levels in the slowly distributing (deep) peripheral compartment and response of the heart to digoxin, as measured by changes in the QS2 index δQS2I. Although it was not possible to distinguish clearly a linear from a nonlinear relationship between digoxin levels in the deep compartment and δQS2I, the nonlinear relationship gave the best overall fit when both serum digoxin and δQS2I data were fitted simultaneously. The simultaneous fityielded a total body clearance of digoxin of 3.6 ml/min/kg and a terminal t1/2 of 42 hr.

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Author notes

  1. William G. Kramer

    Present address: Department of Pharmaceutics, College of Pharmacy, University of Houston, 77004, Houston, Texas

  2. Mohinder S. Bathala

    Present address: A. H. Robins Research Laboratories, 23220, Richmond, Virginia

Authors and Affiliations

  1. Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, 43210, Columbus, Ohio

    William G. Kramer, Mohinder S. Bathala & Richard H. Reaming

  2. Division of Cardiology, College of Medicine, The Ohio State University, 43210, Columbus, Ohio

    Albert J. Kolibash & Richard P. Lewis

  3. Drug Information Center, The Ohio State University Hospitals, 43210, Columbus, Ohio

    James A. Visconti

Authors
  1. William G. Kramer
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  2. Albert J. Kolibash
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  3. Richard P. Lewis
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  4. Mohinder S. Bathala
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  5. James A. Visconti
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  6. Richard H. Reaming
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Additional information

Supported in part by Philips Roxane Laboratories, Columbus, Ohio, Medicinal Chemistry Training Grant GM-1949 (NIH) for W.G.K, Central Ohio Heart Chapter of AHA and National Heart and Lung Institute Training Grant No. 5-T01-HL05968 for A.J.K., and Clinical Research Center Grant RR-34 (PHS). This article is abstracted in part from a dissertation submitted by W.G.K. to the Graduate School, The Ohio State University, Columbus, Ohio, in partial fulfillment of the Doctor of Philosophy degree requirements.

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Kramer, W.G., Kolibash, A.J., Lewis, R.P. et al. Pharmacokinetics of digoxin: Relationship between response intensity and predicted compartmental drug levels in man. Journal of Pharmacokinetics and Biopharmaceutics 7, 47–61 (1979). https://doi.org/10.1007/BF01059440

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  • DOI: https://doi.org/10.1007/BF01059440

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