Biol. Pharm. Bull. 30(7) 1344—1349 (2007)

amino b-lactam antibiotic. As with other ampicillin prodrugs such as pivampicillin and talampicillin, bacampicillin was developed almost 30 years ago under the hypothesis that the addition of a lipophilic moiety to the hydrophilic ampicillin molecule would improve intestinal absorption of the parent drug. It has been reported that ampicillin exhibits 33—54% bioavailability after oral administration and that bacampicillin increases the oral bioavailability of ampicillin up to approximately 90%. Over the past two decades, a large number of papers have provided evidence that several b-lactam antibiotics are absorbed as potent substrates of an H -coupled peptide transporter (PEPT1) present on the apical membranes of enterocytes. Since ampicillin interacts with PEPT1 to a much lesser extent than other orally active b-lactam antibiotics such as ciclacillin and ceftibuten, the contribution of PEPT1 to ampicillin absorption is thought limited. Although PEPT1 exhibits considerably broad substrate specificities to various peptide-like drugs, it has not been clarified whether it is capable of transporting bacampicillin as a substrate. By introducing a 1 -ethoxycarbonyloxyethyl group into the ampicillin molecule, bacampicillin also acquired the characteristics of a lipophilic organic cation. It is well known that a variety of organic cations are absorbed via specialized transport systems in the small intestine. It is therefore possible that a kind of organic cation transporter is unexpectedly involved in the intestinal absorption of bacampicillin. Caco-2 cells express a large number of transporters with which to handle various endogenous and exogenous organic cations such as azasetron, carnitine, choline, diphenhydramine, guanidine, 1-methyl-4-phenyl-pyridinium, nicotine, and thiamine. This study was undertaken to characterize bacampicillin uptake in Caco-2 cells with special focus on its interaction with various transporters for organic cations.