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Originally published In Press as doi:10.1194/jlr.M500358-JLR200 on January 9, 2006

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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{dagger}, C. Justin Cooke§, Irina P. Miller{dagger}, Waldemar L. Olszewski** and Norman E. Miller1,{dagger}

* Diabetes Modeling Group, Department of Paediatrics, University of Cambridge, Cambridge, UK
{dagger} 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 (kp-if) or its mean residence time in interstitial fluid (MRTif). 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. kp-if averaged 0.75%/h (range, 0.33–1.32), and MRTif 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; kp-if, fractional rate constant for transfer from plasma to interstitial fluid; MRTif, mean residence time in interstitial fluid


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