Toxicologic drug concentrations prediction

When the steady-state concentrations of the drug candidate or a metabolite in systemic circulation, usually first detected from toxicokinetic results from multiple-dose toxicology studies, are substantially higher than predicted from single-dose pharmacokinetic studies... 

These data clearly demonstrate that IPPSF flux profiles can be charactoized by five physical chemical parameters (H-acidity, H-basicity, S-Polarizability, and HjO solubility). The correlation of the AUC of the IPPSF flux profile to these parameters was high = 0.978), an important finding because AUC from skin would be the prime measure of systemic exposure in a toxicological risk assessment and could serve as the input function for a physiologically based pharmacokinetic model for a compound. The IPPSF efflux profile from skin reflected by its AUC has been previously used as the input profile for predicting in vivo human plasma-concentration time profiles after transdermal drug delivery (Riviere, Williams, etal., 1992). 

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