Studies on the reliability of a novel absorption-lipophilicity approach to interpret the effects of the synthetic surfactants on drug and xenobiotic absorption.
Some theoretical principles of the absorption/lipophilicity approach, which attempts to explain the effects of the synthetic surfactants on xenobiotic and drug intestinal absorption, are reviewed and experimentally checked by examining the correlations obtained between "in situ" absorption constants, ka, found in rat colon, and "in vitro" lipophilicity indexes, K', for two compound series (secondary aliphatic amines and phenylalkylamines) in the absence and in the presence of the nonionic surfactant Polysorbate 80, in the intestinal perfusion fluid. Evidence is given for the following actions of the synthetic surfactant: at its critical micelle concentration (CMC), it increases the polarity of the absorbing membrane and, at the same time, it disrupts the aqueous stagnant diffusion layer adjacent to the mucosal barrier. When a supramicellar concentration (SMC) is used, the above actions are almost totally masked by the micellar solubilization of the tested amines, which decreases their absorption constants relative to those found at CMC, as markedly as solute lipophilicity increases. As a consequence of these actions, the correlations between ka and K', which are clearly hyperbolic in free solution, become potential in the presence of the surfactant at its CMC, whereas at SMC a bilinear correlation is obtained. Absorption via lipophilic ionized species seems to take place for both compound series. Mathematical and physicochemical interpretations of this behaviour are outlined, and biopharmaceutical implications of these phenomena are discussed.
Martínez-Coscollá
A
A
Department of Pharmacology and Pharmaceutics of the University of Valencia, Spain.
Miralles-Loyola
E
E
Garrigues
T M
TM
Sirvent
M D
MD
Salinas
E
E
Casabó
V G
VG
D000588:Amines / Q000493:pharmacokinetics; D000818:Animals; D001702:Biopharmaceutics; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000378:metabolism; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects*; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008823:Micelles; D011136:Polysorbates; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet; D013501:Surface-Active Agents / Q000494:pharmacology*; D015262:Xenobiotics / Q000493:pharmacokinetics*
D000588:Amines; D008055:Lipids; D008823:Micelles; D011136:Polysorbates; D013501:Surface-Active Agents; D015262:Xenobiotics