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

Published

Journal Article

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 sec 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 all 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.

Full Text

Duke Authors

Cited Authors

  • Krejcie, TC; Henthorn, TK; Niemann, CU; Klein, C; Gupta, DK; Gentry, WB; Shanks, CA; Avram, MJ

Published Date

  • September 1996

Published In

Volume / Issue

  • 278 / 3

Start / End Page

  • 1050 - 1057

PubMed ID

  • 8819485

Pubmed Central ID

  • 8819485

International Standard Serial Number (ISSN)

  • 0022-3565

Language

  • eng

Conference Location

  • United States