Mass kinetics of apolipoprotein A-I in interstitial fluid after administration of intravenous apolipoprotein A-I/lecithin discs in humans.
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.
Hovorka
Roman
R
Diabetes Modeling Group, Department of Paediatrics, University of Cambridge, UK.
Nanjee
M Nazeem
MN
Cooke
C Justin
CJ
Miller
Irina P
IP
Olszewski
Waldemar L
WL
Miller
Norman E
NE
D000328:Adult; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000493:pharmacokinetics*; D045604:Extracellular Fluid / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D008196:Lymph / Q000737:chemistry; D008297:Male; D010713:Phosphatidylcholines / Q000008:administration & dosage; D012709:Serum Albumin / Q000032:analysis
D016632:Apolipoprotein A-I; D010713:Phosphatidylcholines; D012709:Serum Albumin