Characterization of the oral absorption of some beta-lactams: effect of the alpha-amino side chain group.
The intestinal absorption mechanisms of cefixime, 7-aminocephalosporanic acid (7-ACA) and 6-aminopenicillanic acid (6-APA) were determined from the results of single-pass perfusion experiments in rats by modified boundary layer analysis. The estimated absorption parameters (SEM) were as follows: for cefixime, J*max = 0.016 (0.008) mM, Km = 0.031 (0.015) mM, P*m = 0.184 (0.037), P*c = 0.523 (0.051); for 7-ACA, J*max = 6.39 (1.57) mM, Km = 19.33 (5.64) mM, P*c = 0.33 (0.03) mM; and for 6-APA, P*m = 0.41 (0.11), where J*max is the maximal flux of peptide transport system, Km is the intrinsic Michaelis constant, P*m is the dimensionless membrane permeability, and P*c is the dimensionless carrier permeability. Cefixime was absorbed by a carrier-mediated mechanism because its wall permeability (P*w) was concentration dependent and significantly inhibited by cephradine. A concentration-dependent permeability of 7-ACA was observed, but an inhibition study failed to show significant inhibition by cephradine. The absorptions of 6-APA and penicillin V were not inhibited by cephradine or cefixime. The fractions of dose absorbed of several beta-lactam antibiotics correlated well with their absorption numbers obtained from P*w values in rats. These results further demonstrate that an alpha-amino group is not necessary for transport by the intestinal peptide transporter.
Oh
D M
DM
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Sinko
P J
PJ
Amidon
G L
GL
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D010477:Perfusion; D010539:Permeability; D051381:Rats; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams