Coexistence of passive and carrier-mediated processes in drug transport.
The permeability of biological membranes is one of the most important determinants of the pharmacokinetic processes of a drug. Although it is often accepted that many drug substances are transported across biological membranes by passive transcellular diffusion, a recent hypothesis speculated that carrier-mediated mechanisms might account for the majority of membrane drug transport processes in biological systems. Based on evidence of the physicochemical characteristics and of in vitro and in vivo findings for marketed drugs, as well as results from real-life discovery and development projects, we present the view that both passive transcellular processes and carrier-mediated processes coexist and contribute to drug transport activities across biological membranes.
Sugano
Kiyohiko
K
Pfizer, Research Formulation, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. kiyohiko.sugano@pfizer.com
Kansy
Manfred
M
Artursson
Per
P
Avdeef
Alex
A
Bendels
Stefanie
S
Di
Li
L
Ecker
Gerhard F
GF
Faller
Bernard
B
Fischer
Holger
H
Gerebtzoff
Grégori
G
Lennernaes
Hans
H
Senner
Frank
F
D000818:Animals; D001692:Biological Transport; D001693:Biological Transport, Active; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability; D015195:Drug Design; D006801:Humans; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D004364:Pharmaceutical Preparations