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Initial antipyrine disposition in man is altered by propranolol
Author(s) -
Avram M. J.,
Henthorn T. K.,
Niemann C. U.,
Shanks C. A.,
Krejcie T. C.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.128
Subject(s) - propranolol , pharmacokinetics , pharmacology , sufentanil , disposition , anesthesia , indicator dilution , anesthetic , chemistry , pharmacodynamics , medicine , hemodynamics , cardiac output , psychology , social psychology
Purpose β‐Adrenergic antagonists decrease intravenous (IV) anesthetic dose requirements. The present study determined the effect of propranolol on antipyrine (AP) disposition from the moment of rapid IV injection using a recirculatory pharmacokinetic (PK) model. AP is a physiologic marker that distributes to a volume as large as total body water in a blood flow‐dependent manner and is a surrogate for many lipophilic drugs, including IV anesthetics. Methods AP disposition was determined twice in 5 healthy adult males in this IRB‐approved study, once during a propranolol infusion. After rapid AP injection, arterial blood samples were collected frequently for 2 min and less frequently thereafter. Plasma AP concentrations were measured by HPLC. AP disposition was characterized, using SAAM II, by a recirculatory PK model that describes drug disposition from the moment of injection. Parameters were compared using the paired t‐test. Results The disposition of concomitantly administered indocyanine green (ICG) demonstrated that propranolol decreased cardiac output (C.O.) at the expense of the fast peripheral (nonsplanchnic) intravascular circuit. AP AUC was doubled for at least the first 3 min after rapid IV injection due to both decreased C.O. 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. Conclusion The increase in AP AUC due to the propranolol‐induced alteration of initial AP disposition could explain decreased IV anesthetic dose requirements in the presence of β‐adrenergic blockade. Clinical Pharmacology & Therapeutics (2004) 75 , P34–P34; doi: 10.1016/j.clpt.2003.11.128