TY - JOUR T1 - Disposition of Dodecanedioic Acid in Humans JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 846 LP - 852 VL - 292 IS - 3 AU - Alessandro Bertuzzi AU - Geltrude Mingrone AU - Alberto Gandolfi AU - Aldo Virgilio Greco AU - Serenella Salinari Y1 - 2000/03/01 UR - http://jpet.aspetjournals.org/content/292/3/846.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -