Differences in the enhancing effects of sodium caprate on colonic and jejunal drug absorption.
We examined the enhancing effect of sodium caprate (C10) on the jejunal absorption of a poorly absorbed drug, cefmetazole, in rats, in comparison with its colonic absorption (Pharm. Res. 5, 341-346, 1988). Jejunal absorption was significantly enhanced by C10, but to a smaller extent than colonic absorption. Membrane perturbation, caused by the interaction between C10 and membrane proteins or lipids, was shown to increase transcellular drug permeability, as reported in the colon. Paracellular permeabilities, obtained from the permeabilities of water-soluble nonelectrolytes of various molecular weights, showed a two-phase pattern against their free diffusion coefficients, suggesting the existence of at least two pore routes similar to those in the colon. C10 increased paracellular permeability in the colon but not in the jejunum. Impedance analysis and voltage clamp technique in the jejunum showed no significant effect of C10 on paracellular permeability, such as found in the colon. Accordingly, the difference in the effects of C10 on the jejunal and colonic absorption of cefmetazole was due mainly to the difference in its effects on the paracellular pathway.
Tomita
M
M
Department of Biopharmaceutics, Tokyo College of Pharmacy, Japan.
Sawada
T
T
Ogawa
T
T
Ouchi
H
H
Hayashi
M
M
Awazu
S
S
D000818:Animals; D015311:Cefmetazole / Q000493:pharmacokinetics*; D002463:Cell Membrane Permeability / Q000187:drug effects; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D003652:Decanoic Acids / Q000494:pharmacology*; D004357:Drug Synergism; D004553:Electric Conductivity; D005454:Fluorescence Polarization; D007408:Intestinal Absorption / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008563:Membrane Lipids / Q000502:physiology; D008565:Membrane Proteins / Q000187:drug effects; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D003652:Decanoic Acids; D008563:Membrane Lipids; D008565:Membrane Proteins; D015311:Cefmetazole; C031071:decanoic acid