Disposition of dodecanedioic acid in humans

The disposition of dodecanedioic acid (C12) was investigated in six overnig ht-fasting healthy male volunteers, who received a 165-min i.v. infusion of 42.45 mmol of C12 added to 150 mu Ci of [1-12-C-14]C12. Blood samples were collected up to 360 min after the start of infusion, and concentration of serum labeled C12 was determined. Expired radioactivity (mu Ci/min) was mea sured 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 unde r the curve of measured (CO2)-C-14 expiration rate. C12 kinetics was descri bed 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. Th e 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. Para meters of model B were estimated for each subject, whereas model A was iden tified by fitting the pooled data of all subjects. On the basis of estimate s obtained from model B, an average calorie delivery of 500 kcal/day was pr edicted 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 +/- 0.0 8 mmol/min, with a maximal calorie delivery of 750 kcal/day. These results appear promising for C12 utilization in parenteral nutrition, because C12 e limination with urine is low, whereas tissue uptake and oxidation are rathe r efficient.