Safety evaluation of certain food additives - ipcs inchem

42 ETHYL LAUROYL ARGINATE
The median time at which the Cmax of ethyl lauroyl arginate occurred
increased with increasing dose level, indicating a rapid absorption (0.5 h) at
40 mg/kg bw and a more prolonged absorption (3 h) at 320 mg/kg bw. Plasma
concentrations of ethyl lauroyl arginate were below the limit of quantification
by 8 h post-dosing in all animals at all dose levels. Plasma concentrations of
N -lauroyl-L-arginine at 8 h post-dosing were quantifiable in all animals at the 120
and 320 mg/kg bw dose levels. The rate of systemic exposure to ethyl lauroyl
arginate, as characterized by the Cmax ratios at each dose, was low and did not
increase consistently with increasing dose. The extent of systemic exposure to ethyl
lauroyl arginate, as characterized by the AUC8 ratios at each dose, could not be
estimated owing to the small number of quantifiable samples, which was ascribed
to the rapid hydrolysis of ethyl lauroyl arginate and N -lauroyl-L-arginine. The Cmax
and AUC8 ratios of N -lauroyl-L-arginine increased by less than the proportionate
dose increment over the dose range 40–320 mg/kg bw. The authors concluded that
this suggested non-linear (dose-dependent) kinetics, as increasing the dose of ethyl
lauroyl arginate above 40 mg/kg bw resulted in a lower systemic exposure than
would be predicted from a linear relationship. Plasma concentrations of N -lauroyl-
L-arginine were considerably higher than those of ethyl lauroyl arginate, indicating
extensive conversion to N -lauroyl-L-arginine. The terminal rate constant and halflife
could not be estimated from the available data for either ethyl lauroyl arginate
or N -lauroyl-L-arginine for any animal, except for N -lauroyl-L-arginine in one male
receiving 40 mg/kg bw, where k was 0.7123/h and t½ was 1 h.
The effect of the different formulations at a dose level of 120 mg/kg bw are
summarized in Table 2.
Table 2. Pharmacokinetic parameters following different formulations of a
single oral (gavage) dose of ethyl lauroyl arginate (120 mg/kg bw)
administered to male rats
Formulation Cmax (ng/ml) / Tmax (h) AUC8 (ng·h/ml)
Propylene glycol/
water
Ethyl lauroyl arginate N -Lauroyl-Larginine
1.23 ± 0.29 / 1 23.2 ± 2.5 /
0.75
Ethyl lauroyl
arginate
N -Lauroyl-Larginine
– a 103 ± 8
Glycerol/water 9.42 ± 3.54 / 0.75 28.8 ± 4.6 / 1 12.6 ± 4.5 115 ± 18
Water 10.6 ± 6.4 / 0.75 31.2 ± 6.4 / 0.5 8.78 ± 2.12 109 ± 10
a Could not be calculated owing to the small number of quantifiable samples.
Absorption of ethyl lauroyl arginate was rapid, as indicated by the Cmax values
at 0.75–1 h. Plasma concentrations of ethyl lauroyl arginate were below the limit of
quantification (