Adipose drug partitioning

Olive oil was the original model lipid for partition studies, and was used by Overton in his pioneering research [518,524], It fell out of favor since the 1960s, over concerns about standardizing olive oil from different sources. At that time, octanol replaced olive oil as the standard for partition coefficient measurements. However, from time to time, literature articles on the use of olive oil appear. For example, Poulin et al. [264] were able to demonstrate that partition coefficients based on olive oil-water better predict the in vivo adipose-tissue distribution of drugs, compared to those from octanol-water. The correlation between in vivo log Kp (adipose tissue-plasma) and log (olive oil-water) was 0.98 (r2), compared to 0.11 (r2) in the case of octanol. Adipose tissue is white fat, composed mostly of triglycerides. The improved predictive performance of olive oil may be due to its triglyceride content. 

Poulin, R Schoenlein, K. Theil, F.-P., Prediction of adipose tissue Plasma partition coefficients for structurally unrelated drugs, J. Pharm. Sci. 90, 4364-47 (2001). 

Support for these results comes from a paper in which the partitioning of 17 dmgs into adipose tissue was examined [84]. For these drugs, log Poct, log Doct atpH 74, and the retention time on an immobilized artificial membrane, log k IAM, were determined. The adipose storage index (ASI) was defined as ... 

Drugs with low partition coefficients are likely to distribute in the plasma and thus are more likely to have peripheral effects. They are also more likely to be eliminated by renal fdtration. In contrast, those with high partition coefficients will distribute in adipose tissue and are more likely to cross the blood-brain barrier and distribute into the central nervous system (CNS), with CNS effects. These drugs are likely to undergo hepatic metabolism and be eliminated in the bile. 

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