Bioavailability of amoxicillin and clavulanic acid from extended release tablets depends on intragastric tablet deposition and gastric emptying

Abstract

The rate and extent of amoxicillin and clavulanic acid absorption from pharmacokinetically enhanced extended release (ER) tablets is strongly influenced by the intake conditions. In order to investigate the cause of the food effects, a pharmacokinetic study with simultaneous imaging of the in vivo behaviour of the ER tablets by magnetic marker monitoring (MMM) was performed. Under fasting conditions the amoxicillin AUC (1854 ± 280 μg min ml −1) was significantly lower than after intake at the beginning of the breakfast (2452 ± 354 μg min ml −1) or after the breakfast (2605 ± 446 μg min ml −1). In contrast, clavulanic acid AUC was well comparable after tablet intake under fasting conditions and intake at the beginning of a breakfast (191 ± 46 and 189 ± 44 μg min ml −1, respectively) but significantly lower following a breakfast (126 ± 71 μg min ml −1). The localization data showed that the reduced bioavailability of amoxicillin under fasting conditions is due to early gastric emptying in combination with poor absorption from deeper parts of the small intestine. Prolonged gastric residence of clavulanic acid caused by intragastric tablet deposition in the proximal stomach was identified as the reason for the decreased bioavailability of clavulanic acid after tablet intake following the meal.