THE EFFECT OF PROTEIN-BINDING AND LIPOPHILICITY OF PENICILLINS ON THEIR IN-VITRO FLUX ACROSS GASTRIC-MUCOSA

Delivery of amoxycillin across the human gastric mucosa to Helicobacte r pylori is poor compared with that of metronidazole and clarithromyci n, limiting the clinical effectiveness of this penicillin. To investig ate the physicochemical properties of penicillins that influence their flux across gastric mucosa, the fluxes of metronidazole and eight pen icillins were measured in vitro across rat gastric mucosa. The lipophi licity of these drugs was also measured using potentiometric titration . The mean fluxes of monobasic penicillins (range 0.66-0.89 nmol/cm(2) /h) were significantly lower than those of the aminopenicillins (range 1.94-2.80 nmol/cm(2)/h) (P < 0.005). Penicillin flux was not signific antly correlated with lipophilicity as measured, but was significantly correlated with published protein binding data (r(s) = 0.9048, P < 0. 002). Metronidazole flux was significantly higher than that of any pen icillin at 22.6 (+/-0.9) nmol/cm(2)/h (P < 0.001). Therefore, the in-v itro gastric delivery of penicillins can be predicted from protein bin ding which may in turn predict activity against H. pylori in vivo.