## Figure 31

Factors that affect drug concentration at its site of action. Once a drug has been absorbed into the blood, it may be subjected to varying degrees of metabolism, storage in nontarget tissues, and excretion. The quantitative importance of each of these processes for a given drug determines the ultimate drug concentration achieved at the site of action.

ionization will influence their lipid-water partition coefficient and hence their ability to diffuse through membranes.

The proportion of the total drug concentration that is present in either ionized or un-ionized form is dictated by the drug's dissociation or ionization constant (K) and the local pH of the solution in which the drug is dissolved.

The dissociation of a weak acid, RH, and a weak base, B, is described by the following equations:

If these equations are rewritten in terms of their dissociation constants (using Ka for both weak acids and weak bases), we obtain

By taking logarithms and then substituting the terms pK and pH for the negative logarithms of Ka and [H+], respectively, we arrive at the Henderson-Hasselbach equations:

It is customary to describe the dissociation constants of both acids and bases in terms of pKa values. This is possible in aqueous biological systems because a simple mathematical relationship exists between pKa, pKb, and the dissociation constant of water pKw.

The use of only pKa values to describe the relative strengths of either weak bases or weak acids makes comparisons between drugs simpler. The lower the pKa value (pKa < 6) of an acidic drug, the stronger the acid (i.e., the larger the proportion of ionized molecules). The higher the pKa value (pKa > 8) of a basic drug, the stronger the base. Thus, knowing the pH of the aqueous medium in which the drug is dissolved and the pKa of the drug, one can, using the Henderson-Hasselbach equation, calculate the relative proportions of ionized and un-ionized drug present in solution. For example, when the pKa of the drug (e.g., 7) is the same as the pH (e.g., 7) of the surrounding medium, there will be equal proportions of ionized [R-] and un-ionized [RH] molecules; that is, 50% of the drug is ionized.

The effect of pH on drug ionization is shown in Figure 3.3. The relationship between pH and degree of drug ion-ization is not linear but sigmoidal; that is, small changes in pH may greatly influence the degree of drug ionization, especially when pH and pKa values are initially similar.

## Bacterial Vaginosis Facts

This fact sheet is designed to provide you with information on Bacterial Vaginosis. Bacterial vaginosis is an abnormal vaginal condition that is characterized by vaginal discharge and results from an overgrowth of atypical bacteria in the vagina.

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