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Journal of Lipid Research, Vol. 47, 975-981, May 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Mass kinetics of apolipoprotein A-I in interstitial fluid after administration of intravenous apolipoprotein A-I/lecithin discs in humans

Roman Hovorka^*, M. Nazeem Nanjee, C. Justin Cooke, Irina P. Miller, Waldemar L. Olszewski^** and Norman E. Miller^1,

^* Diabetes Modeling Group, Department of Paediatrics, University of Cambridge, Cambridge, UK
Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT
Chesterfield Royal Infirmary, Chesterfield, UK
^** Medical Research Center, Polish Academy of Sciences, Warsaw, Poland

¹ To whom correspondence should be addressed. e-mail: n.e.miller{at}btinternet.com

Apolipoprotein kinetics are customarily determined by modeling time curves of specific radioactivity or isotopic enrichment in plasma after intravenous infusion of radiolabeled lipoproteins or stable isotope-enriched amino acids. However, this provides no information on the fractional rate of transfer of the apolipoprotein from plasma to interstitial fluid (k_p-if) or its mean residence time in interstitial fluid (MRT_if). To determine these parameters for a pharmacologic dose of exogenous apolipoprotein A-I (apoA-I) given intravenously as apoA-I/lecithin discs, we measured apoA-I in plasma and prenodal leg lymph in five healthy men before, during, and after a 4 h infusion at 10 mg/kg/h. ApoA-I concentrations in plasma and lymph were modeled by linear compartmental models (SAAM II version 1.1), using lymph albumin to adjust for the effects of variations in lymph flow rate. k_p-if averaged 0.75%/h (range, 0.33–1.32), and MRT_if averaged 29.1 h (14.1–40.0). Neither parameter was correlated with the distribution volume (57–105 ml/kg) or the fractional elimination rate (1.44–2.91%/h) of apoA-I, determined by modeling plasma apoA-I concentration alone. Although used here to study the mass kinetics of apoA-I, if combined with infusion of a tracer, analysis of lymph could also expand the modeling of endogenous apolipoprotein kinetics.

Supplementary key words high density lipoprotein • interstitium • lipoprotein • lymph • tissue fluid

Abbreviations: apoA-I, apolipoprotein A-I; IF, interstitial fluid; k_p-if, fractional rate constant for transfer from plasma to interstitial fluid; MRT_if, mean residence time in interstitial fluid

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