Kinetics of dodecanedioic acid triglyceride in rats

The kinetics of the triglyceride of dodecanedioic acid (TGDA) has been inve stigated in 30 male Wistar rats after a rapid intravenous bolus injection. TGDA and its product of hydrolysis, nonesterified dodecanedioic acid (NEDA) , were measured in plasma samples taken at different times using an improve d high-performance liquid chromatographic method. The 24-h urinary excretio n of TGDA was 1.54 +/- 0.37 mu mol, corresponding to similar to 0.67% of th e administered amount. Several kinetics models were considered, including c entral and peripheral compartments for the triglyceride and the free forms and expressing transports between compartments with combinations of linear carrier-limited, or time-varying mechanisms. The parameter estimates of the kinetics of TGDA and of NEDA were finally obtained using a three-compartme nt model in which the transfer of TGDA to NEDA was assumed to be linear, th rough a peripheral compartment, and the tissue uptake of NEDA was assumed t o be carrier limited. TGDA had a large volume of distribution (similar to 0 .5 l/kg body wt) with st fast disappearance rate from plasma (0.42 min-l), whereas NEDA had a very small volume of distribution (similar to 0.04 l/kg body wt) and a tissue uptake with maximal transport rate of 0.636 mM/min. I n conclusion, this first study on the triglyceride form of dodecanedioic ac id indicates that it is rapidly hydrolyzed and that both triglyceride and n onesterified forms are excreted in the urine to a very low extent. The tiss ue uptake rate of NEDA is consistent with the possibility of achieving subs tantial energy delivery, should it be added to parenteral nutrition formula tions. Furthermore, the amount of sodium administered with the triglyceride form is one-half of that necessary with the free diacid.