Differential lipid affinity of xenobiotics and natural compounds.

Octanol-1/water partitioning currently provides the most widely used model system to simulate both phospholipid target lipids and triglyceride storage lipids. A differentiation between the two lipid classes is now achieved by making use of a water-induced lipid phase separation. Coefficients (K(TG/PC)) for partitioning between trioleoylglycerol (TG) and phosphatidylcholine (PC) were determined for 20 xenobiotics and two biological lipids. K(TG/PC) values are related to KOW through the relationship, log K(TG/PC)=0.33 log KOW-1.078. The present results will allow better predictions on whether drugs and xenobiotics are bioaccumulated, degraded or reach toxicity-related sites. In addition, applications to natural lipophilic compounds and disease-related proteins are discussed.