Prediction of Oral Absorption of Cephalosporins in Humans

Orally active cephalosporin antibiotics are known to be absorbed from the small intestine via the oligopeptide transporter (PepT1). Although several methods have been proposed for the prediction of oral absorption in humans, no in vitro method has been established to predict oral absorption of the drugs that are absorbed by a carrier-mediated process. In this mini review, we propose a method to predict oral absorption of cephalosporins in humans from in vitro studies using rat intestinal brush border membrane vesicles (BBMV) or Caco-2 cells. Uptake into BBMV or Caco-2 cells via PepT1 was estimated by subtracting the uptake at 4°C from that at 25°C (BBMV) or 37°C (Caco-2 cells), which was well correlated with the extent of oral absorption according to the complete radial mixing (CRM) model reported by Amidon et al. The present method gives fairly good prediction of oral absorption of cephalosporins and may be used for the screening of well absorbed PepT1 substrates.