Oral absorption of cephalosporins is quantitatively predicted from in vitro uptake into intestinal brush border membrane vesicles

In order to establish a method to predict oral absorption of drugs. which a re absorbed by the oligopeptide transporter (PepT1), fraction absorbed (F) of cephalosporin antibiotics was predicted from in vitro uptake into rat in testinal brush border membrane vesicles (BBMV). Using in vitro uptake data. F values of cephalosporins in humans were predicted using the equation der ived from the complete radial mixing (CRM) model, which was proposed by Ami don et al. (Amidon et at.. J. Pharm. Sci. 69 (1980) 1369). In the present s tudy. uptake into BBMV was measured at 25 and 4 degreesC in the presence of an H+-gradient, and the uptake clearance (CLuptake) was calculated. Cleara nce for the uptake mediated by PepT1 (Delta CLuptake) was then calculated a s CLuptake at 25 degreesC minus that at 4 degreesC. When Delta CLuptake and F values were analyzed according to the present equation. fairly good corr elation between Delta CLuptake and F was observed. It was further demonstra ted that the present method may be able to quantitatively predict F values of cephalosporins by using several cephalosporins as standards. (C) 2001 El sevier Science B.V. All rights reserved.