Ionisation of drugs in solution

Many drugs are either weak organic acids (for example, acetylsalicylic acid [aspirin]) or weak organic bases (for example, procaine), or their salts (for example, ephedrine hydrochloride). The degree to which these drugs are ionised in solution is highly dependent on the pH. The exceptions to this general statement are the nonelectrolytes, such as the steroids, and the quaternary ammonium compounds, which are completely ionised at all pH values and in this respect behave as strong electrolytes. The extent of ionisation of a drug has an important effect on its absorption, distribution and elimination and there are many examples of the alteration of pH to change these properties. The pH of urine may be adjusted (for example by administration of ammonium chloride or sodium bicarbonate) in cases of overdosing with amfetamines, barbiturates, narcotics and salicylates, to ensure that these drugs are completely ionised and hence readily excreted. Conversely, the pH of the urine may be altered to prevent ionisation of a drug in cases where reabsorption is required for therapeutic reasons. Sulfonamide crystal-luria may also be avoided by making the urine alkaline. An understanding of the relationship between pH and drug ionisation is of use in the prediction of the causes of precipitation in admixtures, in the calculation of the solubility of drugs and in the attainment of optimum bioavailability by maintaining a certain ratio of ionised to unionised drug. Table 3.5 shows the nominal pH values of some body fluids and sites, which are useful in the prediction of the percentage ionisation of drugs in vivo.

3.5.1 Dissociation of weakly acidic and basic drugs and their salts

According to the Lowry-Bronsted theory of acids and bases, an acid is a substance which w =

Table 3.5 Nominal pH values of some body fluids and sitesa

Site

Nominal pH

Aqueous humour

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