Drug-phospholipid interactions. 2. Predicting the sites of drug distribution using n-octanol/water and membrane/water distribution coefficients.
The in vivo tissue distribution of seventeen drugs has been modeled by using estimated n-octanol/water and membrane/water distribution coefficients. In this study, the membrane affinities are estimated using the new technique of immobilized artificial membrane (IAM) column chromatography. delta (log D(n-octanol/water-membrane/water)), which measures a hypothetical equilibrium of the drug between of n-octanol and membrane phase, is a better model of in vivo tissue distribution, as measured by Adipose Tissue Storage Index (ASI), than either n-octanol/ water or membrane/water distribution coefficients alone. This demonstrates the importance of membrane distribution coefficients as a complementary descriptor of lipophilicity to n-octanol/water distribution coefficients, in modeling in vivo distribution of drugs. This rapid method for predicting in vivo distribution of drugs, based on n-octanol and membrane/water distribution coefficients, may be a useful tool to aid the selection of drugs with beneficial pharmacokinetic profiles.
Barton
P
P
Department of Physical and Metabolic Sciences, Astra Chamwood, Loughborough, Leicestershire, United Kingdom.
Davis
A M
AM
McCarthy
D J
DJ
Webborn
P J
PJ
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D007700:Kinetics; D008567:Membranes, Artificial; D008954:Models, Biological; D000442:Octanols / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D051381:Rats; D014867:Water / Q000737:chemistry
D007202:Indicators and Reagents; D008567:Membranes, Artificial; D000442:Octanols; D004364:Pharmaceutical Preparations; D010743:Phospholipids; D014867:Water