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The pharmacokinetics of penicillamine in a female mongrel dog

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Abstract

The pharmacokinetic parameters of D-penicillamine were investigated by administering four intravenous bolus doses, four oral doses, and six constant rate intravenous infusions to a female mongrel dog at dosages comparable to 250, 500, 750, and 1000 mg in man. The pharmacokinetics of D-penicillamine demonstrated nonlinearity in the dog. There was more than proportional increase in the area under the whole blood concentration curve for an increase in the bolus intravenous dose. The steady state whole blood, plasma, and packed cell levels of penicillamine were increased more than proportionately for an increase in the intravenous infusion rate. Total body clearance of penicillamine was decreased by increasing the dose or the infusion rate of penicillamine. Correspondingly, the estimated half-life of unchanged penicillamine in the whole blood was decreased for increased intravenous bolus doses. The renal clearance of penicillamine was nonlinear, decreasing with time during the bolus experiments and increasing at higher infusion rates. The nonrenal clearance was decreased at higher infusion rates, suggesting that a saturable nonrenal elimination process exists for penicillamine in the dog. The nonlinearities that were observed in the dog, if also present in man, may be responsible in part for the dose related side effects reported clinically for penicillamine.

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Author notes

  1. Richard F. Bergstrom

    Present address: Lilly Research Laboratories, Lilly Laboratory for Clinical Research, Wishard Memorial Hospital, 46202, Indianapolis, Indiana

  2. Donald R. Kay

    Present address: Division of Immunology and Rheumatology, Department of Medicine, University of Missouri, Columbia, Missouri

Authors and Affiliations

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

    Richard F. Bergstrom & John G. Wagner

  2. Rackham Arthritis Research Unit and Upjohn Center for Clinical Pharmacology, The University of Michigan, 48109, Ann Arbor, Michigan

    Donald R. Kay

Authors
  1. Richard F. Bergstrom
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  2. Donald R. Kay
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  3. John G. Wagner
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Additional information

1980–1981 American Foundation for Pharmaceutical Education Manufacturing and Industrial Pharmacy Fellow

This research was supported in part by a National Institutes of Health Grant (AM-20557-02-51).

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Bergstrom, R.F., Kay, D.R. & Wagner, J.G. The pharmacokinetics of penicillamine in a female mongrel dog. Journal of Pharmacokinetics and Biopharmaceutics 9, 603–621 (1981). https://doi.org/10.1007/BF01061028

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  • DOI: https://doi.org/10.1007/BF01061028

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