Simulation, estimating bioavailability using

The original proposal of the approach, supported by a Monte Carlo simulation study [36], has been further validated with both pre-clinical [38, 39] and clinical studies [40]. It has been shown to be robust and accurate, and is not highly dependent on the models used to fit the data. The method can give poor estimates of absorption or bioavailability in two sets of circumstances (i) when the compound shows nonlinear pharmacokinetics, which may happen when the plasma protein binding is nonlinear, or when the compound has cardiovascular activity that changes blood flow in a concentration-dependent manner or (ii) when the rate of absorption is slow, and hence flip-flop kinetics are observed, i.e., when the apparent terminal half-life is governed by the rate of drug input. 

Element uptake from soil and transfer into the edible parts of plants have been addressed in several other studies. Soil-to-plant transfer factors in fruit and vegetables grown in various agricultural conditions have been determined for, for example, Pt [100], T1 [101], and various other metal contaminants [102], In a study on stable isotopes of fission product elements (Ce, Cs, Sr), an in vitro enzy-molysis method has been applied to investigate the solubilization of the analytes from fodder in a simulated ruminant digestion [103], The effect of inhibitors of fission product solubility was also considered and essential elements were determined simultaneously to evaluate potential nutrition problems for the animals from the use of such inhibitors. Selective leaching of individual classes of metal complexes with different ligands and sequential enzymolysis have been recently applied to estimate the potential bioavailability to humans of Cd and Pb in cocoa powder and related products [104]. 

Recent advances made using simulated body fluids to examine the bioavailability of metals are highly valuable and provide a better picture of the risks associated with environmental exposures. In examining the bioavailability of PGE upon inhalation, Columbo et al. (2008a) exposed various simulated lung fluids to road dust, milled vehicle catalyst and solic PGE hydroxides to estimate the metal amounts solubilised in the human respiratory tract. Of all the test materials, they found that the road dust samples contained the greatest amount of bioavailable PGE when exposed to artificial lysosomal fluid (pH 4.5) (36% of Pt and 88% of Rh was solubilised). For the auto catalyst and hydroxide samples, less than 8 and... 

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