Pharmacokinetic analysis of dodecanedioic acid in humans from bolus data

JPEN J Parenter Enteral Nutr. 1995 Nov-Dec;19(6):498-501. doi: 10.1177/0148607195019006498.

Abstract

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.

MeSH terms

  • Binding Sites
  • Chromatography, High Pressure Liquid
  • Dicarboxylic Acids / blood
  • Dicarboxylic Acids / pharmacokinetics*
  • Dicarboxylic Acids / urine
  • Humans
  • Injections, Intravenous
  • Kinetics
  • Male
  • Parenteral Nutrition
  • Protein Binding
  • Serum Albumin / metabolism

Substances

  • Dicarboxylic Acids
  • Serum Albumin
  • dodecanedioic acid