Metabolism and pharmacokinetics of ethyl N(alpha)-lauroyl-L-arginate hydrochloride in human volunteers.

The human metabolism and pharmacokinetics of ethyl N(alpha)-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 (14)C-LAE and (13)C-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 4h. 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 1h. Oral doses of (13)C-LAE in propylene glycol were administered to human volunteers at dose levels of 1.5mg/kg (4 subjects) and 2.5mg/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 2h with mean peak levels of 18.2 ng/ml (1.5mg/kg dose) and 23.9 ng/ml (2.5mg/kg dose). Maximum concentrations of (13)C-arginine occurred earlier (0.5 to 1h) and at much higher levels than LAS with mean peak levels of 124 ng/ml (1.5mg/kg dose) and 240 ng/ml (2.5mg/kg dose). The results showed that in humans LAE was rapidly metabolized to the naturally occurring dietary components lauric acid and arginine.

Cellular effects of monohydrochloride of L-arginine, N-lauroyl ethylester (LAE) on exposure to Salmonella typhimurium and Staphylococcus aureus.

AIMS: Here we study the effect of monohydrochloride of L-arginine, N(alpha)-lauroyl ethylester (LAE), a cationic preservative derived from lauric acid and arginine, on the cell envelopes of Salmonella typhimurium and Staphylococcus aureus at sub-lethal concentration such as their respective minimal inhibitory concentrations, 32 and 8 microg ml(-1), respectively. METHODS AND RESULTS: Bacterial populations were studied by using transmission electron and fluorescence microscopy (TEM and FM), flow cytometry (FC) and ion-flux across the cellular membrane. Cell integrity was altered mainly in the outer membrane of S. typhimurium, but there was no significant change in the cytoplasm. However, in Staph. aureus, clear zones, abnormal septation and mesosome-like structures were observed in the cytoplasm. Bacterial populations were double-stained with propidium iodide (PI) and SYTO-13 for FC analysis. In S. typhimurium the proportion of damaged cells after 24 h was 97% and in Staph. aureus 56.3%. LAE induced transmembrane ion flux, the increase of potassium leakage after 30 min of contact was 7.7 and 3.34 microg ml(-1) for Staph. aureus and S. typhimurium, respectively. Membrane disruption was detected by measuring the proton flow across the membrane. CONCLUSIONS: Disturbance in membrane potential and structural changes was caused by LAE, although cells were not disrupted. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first time the cellular effects of LAE on bacterial cells were studied.