Membrane permeability parameters for some amino acids and beta-lactam antibiotics: application of the boundary layer approach.
The boundary layer approach to analyzing the results of the perfused intestinal segment method of measuring membrane permeabilities is applied to the amino acids; leucine, valine, phenylalanine, lysine and aspartic acid and the beta-lactam antibiotics, cephalexin and penicillin V. The analysis indicates that in determining the membrane parameters, Pw vs. Cw data are preferable to using Jss = PwCw vs. Cw data. It is further shown that the carrier permeability, Pc* = Jmax*/Km, may be the most significant parameter to consider since luminal amino acid or drug concentration may generally be below the Km value. A comparison of P*c values for the beta-lactams with results for passively absorbed compounds indicates that the cephalosporins would be expected to be well absorbed orally based on the perfusion results. This suggests that this approach may be useful in estimating oral drug absorption for compounds that are absorbed passively as well as by a carrier-mediated mechanism.
Hu
M
M
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Sinko
P J
PJ
deMeere
A L
AL
Johnson
D A
DA
Amidon
G L
GL
D000596:Amino Acids / Q000493:pharmacokinetics*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002463:Cell Membrane Permeability; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008433:Mathematics; D010477:Perfusion; D051381:Rats; D047090:beta-Lactams
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D047090:beta-Lactams