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Antibiotic exposure does not influence MRP2 functional expression in Caco-2 cells

Multidrug resistance-associated protein 2 (MRP2) is associated with active drug efflux and may influence oral bioavailability of common classes of drugs. MRP2 expression demonstrates plasticity. Caco-2 cells, a routine in vitro model for predicting oral bioavailability, are often cultured in media containing antibiotics. We have investigated whether exposure of Caco-2 cells to two common antibiotic regimes alters MRP2 functional expression. Caco-2 cells were grown in the presence or absence of either gentamicin or penicillin–streptomycin for up to 9 weeks. MRP2 functional activity was assessed by calcein efflux across the apical membrane. MRP2 protein expression was determined by immunoblots. Neither antibiotic regime resulted in consistent changes in calcein efflux across the apical membrane (reflecting MRP2 activity) or basolateral membrane (reflecting MRP3 and possibly MRP6 activity) of Caco-2 cells. MRP2 protein expression also showed no change in response to antibiotic exposure. Routine exposure of Caco-2 cells to penicillin–streptomycin or gentamicin does not affect apical MRP2 functional activity in intestinal enterocytic Caco-2 cells. Extrapolating these results to the situation in vivo suggests that the oral bioavailability of MRP substrates is not predicted to be influenced by recent courses of antibiotics.