A one-compartment open model is developed at the subcellular level for the disposition phase of pharmacokinetics employing the temporal hierarchy of the processes controlling the destiny of pharmaceuticals in biosystems (absorption, transport, distribution, protein binding, and elimination). The resultant disposition function denotes the intracellular distribution of pharmaceuticals according to their hydrophobicity, acidity or basicity, affinity to proteins, and rate parameters of elimination. The literature data are well fit by structure-activity correlations based on the function that incorporate extra thermodynamic interactions (fixed-time bioactivity-hydrophobicity profiles, kinetics of microbial degradation of organic compounds, and kinetics of analgesic effects of fentanyl derivatives in rats). It is addressed how the method may be used to biosystems of various levels of complexity and serve as a foundation for the development of quantitative structure-time-activity relationships based on models.
Vladlen Slepak
University of Miami Miller School of Medicine, United States
Yong Xiao Wang
Albany Medical College, United States
Consolato M Sergi
Universities of Alberta and Ottawa, Canada
Huiqin Yang
ICON Clinical Research Ltd, United KingdomSubmit your abstract Today
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