Enhanced Elimination

An acid or base load may be provided to a patient and will result in change in the urinary pH. If a substance is present in the blood and it has a pK near the pH of the blood, then this manipulation may change the charge status of the substance. This is shown by the following equations:

Acidify Blood ^ Increased H+ concentration (3.1)

DrugH(0) + OH(-) ^ Drug(-) (negatively charged drug) (3.3)

This technique is also called ion trapping and depends on the fact that charged species are less likely to cross biological membranes. Thus, if the urine is rendered alkaline, an acidic drug such as salicylic acid is converted to a salt within the kidney. This is illustrated by Eq. 3.3. The salicylate anion which carries a negative charge is now more prone to remain in the renal filtrate than to be reabsorbed back into the blood. In other words, it is more rapidly excreted from the body. Converting urine to an alkaline pH is, therefore, an effective means for enhancing the elimination of acids such as salicylates, barbiturates, methotrexate, and others. Conversely, it is possible to increase the acidity of the urine and thereby increase the charged character of drugs which are basic. Basic drugs such as tricyclic antidepressants or phencyc-lidine can be excreted more rapidly by acidifying the urine. This is not recommended, however, because the benefits of improved elimination usually are more than offset by the deleterious effects of the blood acidosis on cardiac and CNS function.

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