PHARMACOKINETIC ANALYSIS OF DODECANEDIOIC ACID IN HUMANS FROM BOLUS DATA

Background: Excretion and tissue uptake of dodecanedioic acid (C 12), a proposed alternative fuel substrate, was investigated in humans by b olus experiments; Methods: Seven overnight-fasting healthy male volunt eers received IV a bolus (1 g) of C12. Blood samples were collected af ter C12 administration at intervals of 15 minutes, and C12 serum conce ntration was measured by high-performance Liquid chromatography. C12 e xcretion in 24-hour urine was measured. Binding of C12 in human serum was determined in separate equilibrium dialysis experiments by means o f an isotopic compound (disodic salt of (1,12)C-14-dodecanedioic acid) . A two-compartment model was used for describing C12 kinetics. Result s: 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 s ites per albumin molecule was 3.1 +/- 0.2 (estimate +/- SE) with an af finity constant of 6.4 +/- 1.8 mM(-1). The distribution volume of cent ral compartment was 5.56 +/- 3.13 L and that of peripheral compartment was 87.4 +/- 30.4 L. The rate constant of exchange between compartmen ts 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: Thes e results are promising for C12 utilization in parenteral nutrition, b ecause C12 elimination in urine is low whereas tissue uptake appears t o be rather efficient.