structured water gives rise to the positive entropy change, which contributes to a negative free-energy change.

10.9.2 Lipophilicity and protein binding

Given the data in Table 10.9 it is not surprising to find that the extent of protein binding of many drugs is a linear function of their partition coefficient P (or log P). A linear equation of the form log(percentage bound/percentage free) = 0.5 log P - 0.665 has been found to be applicable to serum binding of penicillins. Although there may be an electrostatic component to the interaction, the binding increases with the degree of lipophilicity, suggesting, as is often the case, that more than one binding interaction is in force.

Binding to protein outside of the plasma may determine the characteristics of drug action or transport. Muscle protein may bind

Table 10.9 Thermodynamic parameters of binding of drugs

to bovine serum


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