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.
Hawkins
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Huntingdon Life Sciences Ltd., Huntingdon, PE28 4HS, UK. David.drhawkins@btinternet.com
Rocabayera
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Ruckman
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Segret
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Shaw
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D000900:Anti-Bacterial Agents / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005520:Food Preservatives / Q000378:metabolism / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D008297:Male
D000900:Anti-Bacterial Agents; D005520:Food Preservatives; C031371:N(alpha)-lauroylarginine ethyl ester; D001120:Arginine