Disposition of Dodecanedioic Acid in Humans

Abstract

The disposition of dodecanedioic acid (C12) was investigated in six overnight-fasting healthy male volunteers, who received a 165-min i.v. infusion of 42.45 mmol of C12 added to 150 μCi of [1–12-¹⁴C]C12. Blood samples were collected up to 360 min after the start of infusion, and concentration of serum labeled C12 was determined. Expired radioactivity (μCi/min) was measured up to 600 min and at 24 h. The 24-h C12 urinary excretion was around 5% of the administered amount. The percentage of C12 oxidized was 81.7 ± 9.5% (mean ± S.D.) of administered amount as estimated from the area under the curve of measured¹⁴CO₂ expiration rate. C12 kinetics was described by assuming a single compartment. A saturable rate of C12 tissue uptake (model A) and a linear rate of tissue uptake (model B) were considered. The kinetics of CO₂ produced by C12 oxidation was described by a fast pathway acting in parallel to a slow pathway modeled by first order kinetics. Parameters of model B were estimated for each subject, whereas model A was identified by fitting the pooled data of all subjects. On the basis of estimates obtained from model B, an average calorie delivery of 500 kcal/day was predicted in the plateau phase for the infusion rate of our experiments. When estimated from model A, the maximal rate of tissue uptake was 0.38 ± 0.08 mmol/min, with a maximal calorie delivery of 750 kcal/day. These results appear promising for C12 utilization in parenteral nutrition, because C12 elimination with urine is low, whereas tissue uptake and oxidation are rather efficient.