The effect of halothane on the recirculatory pharmacokinetics of physiologic markers

Michael J. Avram*, Tom C. Krejcie, Claus U. Niemann, Cheri Klein, W. Brooks Gentry, Colin A. Shanks, Thomas K. Henthorn

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Background: The cardiovascular effects of halothane are well recognized, but little is known of how this affects drugs distribution. The effect of halothane anesthesia on physiologic factors that affect drug disposition from the moment of injection was investigated. Methods: The dispositions of markers of intravascular space and blood flow (indocyanine green), extracellular space and free water diffusion (inulin), and total body water and tissue perfusion (antipyrine) were determined in four purpose-bred coonhounds. The dogs were studied while awake and while anesthetized with 1%, 1.5%, and 2% halothane in a randomized order determined by a repeated measures Latin square experimental design. Marker dispositions were described by recirculatory pharmacokinetic models based on frequent early and less frequent later arterial blood samples. These models characterize the role of cardiac output and its distribution on drug disposition. Results: Halothane caused a significant and dose-dependent decrease in cardiac output. The disposition of antipyrine was most profoundly affected by halothane anesthesia, which increased both nondistributive intercompartmental clearance and volume while decreasing fast and slow tissue clearances and elimination clearance in a halothane dose-dependent manner. Conclusions: Halothane- induced changes in blood flow to the compartments of the antipyrine recirculatory model were not proportional to changes in cardiac output. Halothane anesthesia significantly increased (to more than double) the area under the drug concentration versus time curve due to an increase in the apparent peripheral blood flow not involved in drug distribution, despite a dose-dependent cardiac output decrease. Recirculatory pharmacokinetic models include the best aspects of traditional compartmental and physiologic pharmacokinetic models while offering advantages over both.

Original languageEnglish (US)
Pages (from-to)1381-1393
Number of pages13
JournalAnesthesiology
Volume87
Issue number6
DOIs
StatePublished - Dec 1997

Keywords

  • Anesthetics, volatile: halothane; influence on recirculatory pharmacokinetics in dogs
  • Blood flow and effect of halothane on drug distribution in dogs
  • Blood volume and effect of halothane on drug distribution in dogs
  • Heart: cardiac output; effect of halothane on drug distribution in dogs
  • Pharmacokinetics models: recirculatory; halothane anesthesia in dogs
  • Pharmacokinetics: distribution; halothane anesthesia in dogs

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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