Pharmacokinetic Analysis of Dodecanedioic Acid in Humans From Bolus Data

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 IV 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 of urinary excretion 25.6 ± 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. (Journal of Parenteral and Enteral Nutrition 19:498-501, 1995)