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Prediction of the plasma concentration time courses of various drugs in humans based on data from rats.

The concentrations of seven drugs, i.e., phenobarbital (PB), phenytoin (DPH), hexobarbital (HXB), quinidine (QD), tolbutamide (TB), valproate (VA), and diazepam (DZP) in human plasma were predicted by a physiologically-based pharmacokinetic model using the intrinsic clearance of unbound drug and the tissue-to-plasma unbound concentration ratios extrapolated from rat data, and the plasma protein binding, blood-to-plasma concentration ratios and physiological parameters in humans. The predicted concentration curves of DPH, HXB, QD and PB in human plasma showed comparatively good agreements with the observed values except for TB, VA and DZP, for which the area under concentration-time curves (AUC) were overestimated or underestimated.