FD-004

We previously reported that beverage-drug interactions can be partly explained by osmotic fluid secretion, leading to drug dilution in the intestine, using adult (8-week-old) rats. In this study, age-related differences in osmolality-dependent fluid dynamics associated with beverage-drug interactions were examined in situ using juvenile (3-week-old) and adult rats. Following administration of apple juice or hyperosmotic mannitol solution (700 mOsm/kg), fluid secretion in the jejunum of juvenile rats was significantly greater than that in adult rats. The concentration of FD-4, a non-permeable compound, in the jejunum was also lower in juvenile rats than in adult rats. Consistent with these differences, the fraction absorbed of atenolol from the jejunum in juvenile rats after administration of hyperosmotic solution was significantly lower than that in adult rats. Interestingly, an osmolarity-dependent increase in chloride levels in the jejunum was observed at the same time, and the effect was greater in juvenile rats than in adult rats, suggesting an age-related difference in chloride secretion. Our studies with juvenile and adult rats indicate that age-related differences exist in luminal fluid secretion following administration of hyperosmotic solutions, potentially leading to changes in the oral absorption of poorly permeable drugs specific to juvenile populations.