Robust assessment of statistical significance in the use of unbound/intrinsic pharmacokinetic parameters in quantitative structure-pharmacokinetic relationships with lipophilicity.
作者： Peter J. H. Webborn , Andrew M. Davis , David W. Salt
DOI:
关键词: Quantitative structure 、 Volume of distribution 、 Chemistry 、 Statistical analysis 、 Lipophilicity 、 Chromatography 、 Biological system 、 Pharmacokinetics 、 Free form
摘要: The optimization of pharmacokinetic properties remains one the most challenging aspects drug design. Key parameters, clearance and volume distribution, are multifactorial, which makes deriving structure-pharmacokinetic relationships difficult. correction distribution for unbound fraction in plasma is approach taken that has enabled quantitative to be derived. Three published data-sets where parameters have been correlated with lipophilicity reanalyzed. reanalysis shown high correlation coefficients can achieved without any true data lead misinterpretation ways influences pharmacokinetics. Randomization procedures proposed as a more robust method assessing significance.
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