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.
Footnotes
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Send reprint requests to: Alessandro Bertuzzi, Istituto di Analisi dei Sistemi ed Informatica del CNR, Viale Manzoni 30, 00185 Rome, Italy. E-mail: bertuzzi{at}iasi.rm.cnr.it
- Abbreviations:
- DA
- dicarboxylic acid
- C12
- dodecanedioic acid
- BMI
- body mass index
- MH
- methylbenzethonium hydroxide
- S.A.
- specific activity
- Received July 7, 1999.
- Accepted November 16, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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