Abstract
The present study was designed to investigate the effect of food and of a raised intragastric pH on the bioavailability of two prodrug beta-lactam, antibiotics, namely bacampicillin and cefuroxime axetil. Six healthy volunteers participated in an intraindividual comparison of absorption of (a) prodrug, (b) breakfast, followed by prodrug, (c) breakfast, ranitidine and sodium bicarbonate followed by prodrug, and (d) ranitidine and sodium bicarbonate, followed by prodrug. All volunteers were dosed with both bacampicillin and cefuroxime axetil under the above regimens. The drug-free periods between trials were 7 days. Blood samples were obtained before and 20, 40, 60, 90, 120, 150, 180, 210 min and 4, 5, 6, 8 and 10 h after administration. The urine was collected for a period of 10 h after dosing with the antibiotic. An estimation of the relative bioavailability of the drugs under the various regimens was made by comparing the average areas under the serum concentration time curves and also the amounts recovered in the urine. Both food and reduced gastric acidity decreased the bioavailability of bacampicillin (as ampicillin) and these variables had an additive lowering effect on the AUC and percentage urinary recovery. Possibly this ester becomes partially hydrolyzed prior to absorption on raising the intragastric pH. Adsorption onto food components or complexing with proteins may also play a role in the reduced bioavailability of bacampicillin in the presence of food. In contrast, the absorption of the cefuroxime ester was enhanced postprandially. This may be rationalized in terms of delayed gastric emptying and gastrointestinal transit which allows more complete dissolution or prolonged residence at the most favourable site of absorption in the intestine.(ABSTRACT TRUNCATED AT 250 WORDS)
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