Passive lipoidal diffusion and carrier-mediated cell uptake are both important mechanisms of membrane permeation in drug disposition.
Recently, it has been proposed that drug permeation is essentially carrier-mediated only and that passive lipoidal diffusion is negligible. This opposes the prevailing hypothesis of drug permeation through biological membranes, which integrates the contribution of multiple permeation mechanisms, including both carrier-mediated and passive lipoidal diffusion, depending on the compound's properties, membrane properties, and solution properties. The prevailing hypothesis of drug permeation continues to be successful for application and prediction in drug development. Proponents of the carrier-mediated only concept argue against passive lipoidal diffusion. However, the arguments are not supported by broad pharmaceutics literature. The carrier-mediated only concept lacks substantial supporting evidence and successful applications in drug development.
4 The Maltings, Walmer, Kent, CT14 7AR, U.K.
Dennis
D
Smith
Per
P
Artursson
Alex
A
Avdeef
Li
L
Di
Gerhard F
GF
Ecker
Bernard
B
Faller
J Brian
JB
Houston
Manfred
M
Kansy
Edward H
EH
Kerns
Stefanie D
SD
Krämer
Hans
H
Lennernäs
Han
H
van de Waterbeemd
Kiyohiko
K
Sugano
Bernard
B
Testa
D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology*; D004058:Diffusion; D004337:Drug Carriers / Q000378:metabolism*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D004337:Drug Carriers; D004364:Pharmaceutical Preparations