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1 Biomathematics Laboratory,
The kinetics of the
triglyceride of dodecanedioic acid (TGDA) has been investigated 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
improved high-performance liquid chromatographic method. The 24-h
urinary excretion of TGDA was 1.54 ± 0.37 µmol, corresponding to
~0.67% of the administered amount. Several kinetics models were
considered, including central 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-compartment model
in which the transfer of TGDA to NEDA was assumed to be linear, through
a peripheral compartment, and the tissue uptake of NEDA was assumed to
be carrier limited. TGDA had a large volume of distribution (~0.5
l/kg body wt) with a fast disappearance rate from plasma (0.42 min
1), whereas NEDA had a
very small volume of distribution (~0.04 l/kg body wt) and a tissue
uptake with maximal transport rate of 0.636 mM/min. In conclusion, this
first study on the triglyceride form of dodecanedioic acid indicates
that it is rapidly hydrolyzed and that both triglyceride and
nonesterified forms are excreted in the urine to a very low extent. The
tissue uptake rate of NEDA is consistent with the possibility of
achieving substantial energy delivery, should it be added to parenteral
nutrition formulations. Furthermore, the amount of sodium administered
with the triglyceride form is one-half of that necessary with the free diacid.
dicarboxylic acids; triglyceride of dodecanedioic acid
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