Isomers binding differences between

The extent of binding differences between isomers is most readily noted from ratios of fractions free in the plasma this ratio can be as high as three (Table 2). Recognizing that plasma protein binding impacts on drug distribution and elimination, differences in plasma protein binding between stereoisomers may lead to misinterpretation of pharmacokinetic comparisons between isomers, unless protein binding of the isomers is considered. 

There are both geometric and kinetic differences between the interactions of A- and A-[Ru(bpy)2(hpimp)]2+ hpimp=2-(2-hydroxyphenyl)imi-dazo [4,5-/]-1,10-phenanthroline and the hexanucleotide d(GTCGAC)2. The A-isomer penetrates more deeply into the major groove of the polynucleotide it also binds more rapidly than the A-isomer to DNA (156). 

This is, in principle, in agreement with extended Hiickel molecular-orbital calculations. The calculated binding energy and difference between the energies of the LUMO and HOMO for the four possible isomers indicate the experimentally isolated structure to be the most stable one, although the extended Hiickel calculation does not show a substantial relative stability (Table I). 

For enantiomeric drugs with low organ clearance, differences in renal or hepatic clearance between stereoisomers may reflect their free fraction in the plasma and not real stereoselectivity of the ability of the organ to remove the free enantiomers (intrinsic clearance) from the plasma. Clearance differences between stereoisomers of verapamil and disopyramide may be a function of plasma protein binding differences. In addition, volumes of distribution as well as concentration ratios of stereoisomers in body fluids to total plasma and blood are influenced by plasma protein binding. For example, the larger volume of distribution and greater total body clearance of R-disopyramide compared to the S isomer may be explained by the lower... 

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