Pharmacokinetic analysis of dodecanedioic acid in humans from bolus data.
BACKGROUND
Excretion and tissue uptake of dodecanedioic acid (C12), a proposed alternative fuel substrate, was investigated in humans by bolus experiments.


METHODS
Seven overnight-fasting healthy male volunteers received i.v. a bolus (1 g) of C12. Blood samples were collected after C12 administration at intervals of 15 minutes, and C12 serum concentration was measured by high-performance liquid chromatography. C12 excretion in 24-hour urine was measured. Binding of C12 in human serum was determined in separate equilibrium dialysis experiments by means of an isotopic compound (disodic salt of (1,12)14C-dodecanedioic acid). A two-compartment model was used for describing C12 kinetics.


RESULTS
The excreted amount of C12 in 24-hour urine was found to be, on the average, 1.62% of administered dose. The apparent number of binding sites per albumin molecule was 3.1 +/- 0.2 (estimate +/- SE) with an affinity constant of 6.4 +/- 1.8 mM-1. The distribution volume of central compartment was 5.56 +/- 3.13 L and that of peripheral compartment was 87.4 +/- 30.4 L. The rate constant of exchange between compartments was 4.60 +/- 3.50 L/min, that or urinary excretion 25.6 +2- 15.5 mL/min, and that of tissue uptake 2.17 +/- 0.86 L/min.


CONCLUSIONS
These results are promising for C12 utilization in parenteral nutrition, because C12 elimination in urine is low whereas tissue uptake appears to be rather efficient.
Bertuzzi
A
A
Istituto di Analisi dei Sistemi ed Informatica del CNR, Roma, Italy.
Mingrone
G
G
Gandolfi
A
A
Greco
A V
AV
Salinari
S
S
D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D003998:Dicarboxylic Acids / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D010288:Parenteral Nutrition; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism
D003998:Dicarboxylic Acids; D012709:Serum Albumin; C036836:dodecanedioic acid