Antagonism of sodium amoxycillin absorption in man following oral administration with glycyl-peptides

The effect of glycyl-peptides on the absorption of amoxycillin sodium was studied in 4 healthy, young adults. Amoxycillin was assayed in urine by HPLC. The initial (0-0.5 h) excretion rate of amoxycillin was significantly (p < 0.05) reduced when 25 mmol diglycine, triglycine, glycylleucine, glycyltyrosine or glycylproline, was administered with 0.25 mmol amoxycillin sodium. The maximum reduction (81%) occurred when amoxycillin was given with glycylproline. Significantly longer mean residence times were observed after administration with glycylleucine, glycyltyrosine and glycylproline, compared with amoxycillin alone. Triglycine (25 mmol) gave similar results to diglycine, but glycine (25 mmol) had no significant effect on amoxycillin absorption. Administration of peptides had no effect on amoxycillin elimination half-life or urine flow rate. A sigmoidal dose-response curve was obtained when glycylproline dose was plotted against reduction in initial amoxycillin excretion rate. Preliminary enzymatic kinetic analyses of these data in 3 subjects gave K(i) values ranging from 3 mmol to 11.5 mmol for glycylproline. Collectively, these results indicated that the absorption of amoxycillin from the human intestine may occur via the carrier system used by di- and tripeptides, but not amino acids