Biophysical absorption models for phenyl-alkyl acids in the absence and in the presence of surfactants. Studies in the rat small intestine.
The present study reviews and checks, by means of experimental work, some theoretical principles of a novel absorption-lipophilicity approach (Pl [symbol: see text] 160-Delfina et al., 1987), used to interpret the effects of synthetic surfactants on drug absorption. For this purpose the correlations between intestinal rat gut absorption constants and lipophilicity indexes are analyzed for a group of compounds belonging to a true homologous series (w-phenyl-alkyl carboxylic acids), in the absence and in the presence of polysorbate 80 in the luminal fluid. Evidence is given for the following surfactant actions: (a) at critical micelle concentration (CMC), the surfactant increases membrane polarity and simultaneously nullifies the limiting character of the stagnant aqueous layer adjacent to the membrane; (b) at supramicellar concentrations (SMC) the above actions become almost completely masked by the micellar solubilization of the compounds, which decreases their absorption rate constants. As a consequence of these interactions, correlation between membrane absorption and lipophilicity, which was clearly hyperbolic in free solution, becomes potential in the presence of surfactant at CMC, whereas at SMC a bilinear correlation is found. Pore absorption was much less affected. Mathematical and physiochemical reasons for this behaviour are outlined, and practical implications are briefly discussed.
Fabra-Campos
S
S
Department of Pharmacology and Pharmaceutics, Faculty of Pharmacy, University of Valencia, Spain.
Real
J V
JV
Gomez-Meseguer
V
V
Merino
M
M
Pla-Delfina
J M
JM
D000818:Animals; D002264:Carboxylic Acids / Q000737:chemistry / Q000493:pharmacokinetics*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D007408:Intestinal Absorption / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008823:Micelles; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains; D013501:Surface-Active Agents / Q000494:pharmacology*; D015262:Xenobiotics / Q000737:chemistry / Q000493:pharmacokinetics*
D002264:Carboxylic Acids; D008823:Micelles; D013501:Surface-Active Agents; D015262:Xenobiotics