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lipophilicity

Figure 9.3 Parabolic nature

of a typical activity-log P

plot: the decrease in biological activity beyond the optimal

log Po probably is due to the factors listed.

If one measures the absorption of a sufficiently wide range of substances in a homologous series, one generally finds that there is an optimal point in the series for absorption. In other words, a plot of percentage absorption versus log P would be parabolic with the optimum value designated as log Po (Fig. 9.3). By noting the values of optimal partition coefficient for different absorbing membranes and surfaces, one can deduce something about their nature. Some values are given in Table 9.1.

The parabolic nature of activity-log P plots is due to a combination of factors: with drugs with high log P values, protein binding, low solubility and binding to extraneous sites cause a lower measured activity than if it were

Table 9.1 Ideal lipophilic character of drugs (log Po) in different regions of the body

System Solute or drug Log Po (octanol/water)

for maximal transport

Buccal cavity (human)

Bases

5.52 (undissociated)

0 0

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