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Pharmaceutical Research

, Volume 28, Issue 5, pp 962–977 | Cite as

Lipophilicity and Its Relationship with Passive Drug Permeation

  • Xiangli Liu
  • Bernard Testa
  • Alfred Fahr
Expert Review

ABSTRACT

In this review, we first summarize the structure and properties of biological membranes and the routes of passive drug transfer through physiological barriers. Lipophilicity is then introduced in terms of the intermolecular interactions it encodes. Finally, lipophilicity indices from isotropic solvent systems and from anisotropic membrane-like systems are discussed for their capacity to predict passive drug permeation across biological membranes such as the intestinal epithelium, the blood-brain barrier (BBB) or the skin. The broad evidence presented here shows that beyond the predictive power of lipophilicity parameters, the various intermolecular forces they encode allow a mechanistic interpretation of passive drug permeation.

KEY WORDS

lipophilicity permeation quantitative structure-permeation relationships 

ABBREVIATIONS

ADME

absorption, distribution, metabolism and excretion

BBB

blood-brain barrier

CHOL

cholesterol

cyc

cyclohexane

DCE

the 1,2-dichloroethane/water system

DCP

dicetylphosphate

DMPC

L-α-dimyristoylphosphatidylcholine

EPC

egg phosphatidylcholine

IAM

immobilized artificial membrane

ILC

immobilized liposome chromatography

LEKC

liposome electrokinetic chromatography

LMVs

large multilamellar vesicles

log D

distribution coefficient

log k

capacity factor

log Kp

permeability coefficients

log P

partition coefficient

LUVs

large unilamellar vesicles

PC

phosphatidylcholine

PE

phosphatidylethanolamine

PS

phosphatidylserine

SC

stratum corneum

SUVs

small unilamellar vesicles

UWL

unstirred water layer

Notes

ACKNOWLEDGMENT

We would like to thank Dr. Sylvio May, North Dakota State University for helpful discussions.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Pharmaceutical TechnologyFriedrich-Schiller-Universität JenaJenaGermany
  2. 2.Pharmacy DepartmentUniversity Hospital Centre, CHUV-BH04LausanneSwitzerland

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