PT  - JOURNAL ARTICLE
AU  - Andrew M. Davis
AU  - Peter J. H. Webborn
AU  - David W. Salt
TI  - Robust Assessment of Statistical Significance in the Use of Unbound/Intrinsic Pharmacokinetic Parameters in Quantitative Structure–Pharmacokinetic Relationships with Lipophilicity
DP  - 2000 Feb 01
TA  - Drug Metabolism and Disposition
PG  - 103--106
VI  - 28
IP  - 2
4099  - http://dmd.aspetjournals.org/content/28/2/103.short
4100  - http://dmd.aspetjournals.org/content/28/2/103.full
SO  - Drug Metab Dispos2000 Feb 01; 28
AB  - The optimization of pharmacokinetic properties remains one of the most challenging aspects of drug design. Key parameters, clearance and volume of distribution, are multifactorial, which makes deriving structure-pharmacokinetic relationships difficult. The correction of clearance and volume of distribution for the unbound fraction in plasma is one approach taken that has enabled quantitative structure-pharmacokinetic relationships to be derived. Three published data-sets where unbound parameters have been correlated with lipophilicity have been reanalyzed. The reanalysis has shown that high correlation coefficients can be achieved without any true correlation in the data and can lead to misinterpretation of the ways in which lipophilicity influences pharmacokinetics. Randomization procedures are proposed as a more robust method of assessing significance. The American Society for Pharmacology and Experimental Therapeutics