Recirculatory pharmacokinetic models of markers of blood, extracellular fluid and total body water administered concomitantly

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


Pharmacokinetic models were developed to describe the disposition of markers of extracellular fluid (inulin) and total body water (antipyrine) from the moment of injection to incorporate the intravascular mixing component, determined by a marker of intravascular space (indocyanine green, ICG). The simultaneous dispositions of these markers were characterized in four halothane-anesthetized dogs. After injection of ICG, [14C]-inulin, and antipyrine into the right atrium, femoral arterial blood samples were collected every 3 sac for 1 min and less frequently to 20 min for ICG and to 360 min for inulin and antipyrine. ICG and antipyrine concentrations were measured by high-performance liquid chromatography and [14C]-inulin concentrations were measured by liquid scintillation counting. The marker concentration histories were characterized completely by fully identifiable recirculatory compartmental models. Because neither ICG nor inulin distribute beyond intravascular space before recirculation, their first-pass data were modelled simultaneously to improve confidence in central circulation model parameters. This central circulation model included an estimate of cardiac output that was retained in the recirculatory models of air markers. Three tissue compartments were identified for antipyrine, a lipid soluble marker that equilibrates with tissue (including the lung) and estimates total body water and tissue blood flow. The hydrophilic marker, inulin, diffuses into interstitial fluid so slowly that only two extravascular compartments were identified. These models may be used to determine how cardiac output and its distribution, pulmonary drug uptake, and nondistributive blood flow contribute to variability in patient response to drugs with a rapid onset of effect.

Original languageEnglish (US)
Pages (from-to)1050-1057
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number3
StatePublished - Sep 1996

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


Dive into the research topics of 'Recirculatory pharmacokinetic models of markers of blood, extracellular fluid and total body water administered concomitantly'. Together they form a unique fingerprint.

Cite this