Role of P‐glycoprotein‐mediated secretion in absorptive drug permeabiity: An approach using passive membrane permeability and affinity to P‐glycoprotein††Dedicated to Prof. B. C. Lippold on the occasion of his 60th birthday.

Abstract It has been shown in vivo and in vitro that P‐glycoprotein (P‐gp) may be able to influence the permeability of its substrates across biological membranes. However, the quantitative contribution of the secretion process mediated by P‐gp on the overall permeability of membranes has not been determined yet. In particular, observations need to be clarified in which substrates showing high affinity to P‐glycoprotein, e.g., verapamil, apparently do not seem to be greatly influenced by P‐gp in their permeability and consequently also with respect to their extent of GI‐absorption after oral administration, whereas weaker substrates of P‐gp, e.g., talinolol, have clearly shown P‐gp‐related …