Metabolism and pharmacokinetics of ethyl Nα-lauroyl-L-arginate hydrochloride in human volunteers

The human metabolism and pharmacokinetics of ethyl Nα-lauroyl-L-arginate hydrochloride (LAE), a new antimicrobial agent for use in foods have been investigated using both in vitro and in vivo techniques with 14C-LAE and 13C-LAE respectively. LAE was readily hydrolysed to the corresponding lauroyl arginine (LAS) on incubation with human plasma samples to the extent of about 50% during 4 h. LAE was stable in simulated gastric fluid but in simulated intestinal fluid it was rapidly hydrolysed to LAS and arginine with more than 90% conversion to arginine after 1 h. Oral doses of 13C-LAE in propylene glycol were administered to human volunteers at dose levels of 1.5 mg/kg (4 subjects) and 2.5 mg/kg (2 subjects). LAE was only detected in two plasma samples in one individual at the higher dose level close to the limit of quantification (1 ng/ml). Maximum plasma concentrations of LAS generally occurred at 2 h with mean peak levels of 18.2 ng/ml (1.5 mg/kg dose) and 23.9 ng/ml (2.5 mg/kg dose). Maximum concentrations of 13C-arginine occurred earlier (0.5 to 1 h) and at much higher levels than LAS with mean peak levels of 124 ng/ml (1.5 mg/kg dose) and 240 ng/ml (2.5 mg/kg dose). The results showed that in humans LAE was rapidly metabolized to the naturally occurring dietary components lauric acid and arginine.