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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

β-Adrenergic Blockade Affects Initial Drug Distribution Due to Decreased Cardiac Output and Altered Blood Flow Distribution

Michael J. Avram, Tom C. Krejcie, Thomas K. Henthorn and Claus U. Niemann
Journal of Pharmacology and Experimental Therapeutics November 2004, 311 (2) 617-624; DOI: https://doi.org/10.1124/jpet.104.070094
Michael J. Avram
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Tom C. Krejcie
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Thomas K. Henthorn
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Claus U. Niemann
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Abstract

β-Adrenergic receptor blockers decrease intravenous anesthetic dose requirements. The present study determined the effect of propranolol on indocyanine green and antipyrine disposition from the moment of rapid intravenous injection. Anti-pyrine is a physiological marker that distributes to a volume as large as total body water in a blood flow-dependent manner and is a pharmacokinetic surrogate for many lipophilic drugs, including intravenous anesthetics. Antipyrine and indocyanine green disposition were determined twice in five healthy adult males in this Institutional Review Board-approved study, once during propranolol infusion. After rapid indocyanine green and antipyrine injection, arterial blood samples were collected frequently for 2 min and less frequently thereafter. Plasma indocyanine green and antipyrine concentrations were measured by high-performance liquid chromatography. Indocyanine green and antipyrine disposition were characterized, using SAAM II, by a recirculatory pharmacokinetic model that describes drug disposition from the moment of injection. Parameters were compared using the paired t test. The disposition of indocyanine green demonstrated that propranolol decreased cardiac output at the expense of the fast peripheral (nonsplanchnic) intravascular circuit. The area under the antipyrine concentration versus time relationship was doubled for at least the first 3 min after injection due to both decreased cardiac output and maintenance of nondistributive blood flow at the expense of a two-thirds reduction of blood flow (intercompartmental clearance) to the rapidly equilibrating (fast, splanchnic) tissue volume. The increase in antipyrine area under the curve due to propranolol-induced alteration of initial antipyrine disposition could explain decreased intravenous anesthetic dose requirements in the presence of β-adrenergic receptor blockade.

Footnotes

  • This study was supported in part by National Institutes of Health Grants GM43776, GM47502, and GM47819.

  • doi:10.1124/jpet.104.070094.

  • ABBREVIATIONS: AUC, area under the curve; ICG, indocyanine green.

  • ↵1 Current address: Department of Anesthesiology, University of Colorado Health Sciences Center, 4200 East Ninth Ave., Campus Box B-113, Denver, CO 80262.

  • ↵2 Current address: University of California at San Francisco, Department of Anesthesia (310), 521 Parnassus Ave., San Francisco, CA 94143.

    • Received April 16, 2004.
    • Accepted June 11, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 311 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 311, Issue 2
1 Nov 2004
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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

β-Adrenergic Blockade Affects Initial Drug Distribution Due to Decreased Cardiac Output and Altered Blood Flow Distribution

Michael J. Avram, Tom C. Krejcie, Thomas K. Henthorn and Claus U. Niemann
Journal of Pharmacology and Experimental Therapeutics November 1, 2004, 311 (2) 617-624; DOI: https://doi.org/10.1124/jpet.104.070094

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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

β-Adrenergic Blockade Affects Initial Drug Distribution Due to Decreased Cardiac Output and Altered Blood Flow Distribution

Michael J. Avram, Tom C. Krejcie, Thomas K. Henthorn and Claus U. Niemann
Journal of Pharmacology and Experimental Therapeutics November 1, 2004, 311 (2) 617-624; DOI: https://doi.org/10.1124/jpet.104.070094
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