For example, alkalinization of urine increases the excretion of the weak acids phenobarbital and aspirin, and acidification may accelerate the excretion of bases, such as methamphetamine. The extent to which changes in urinary pH alter the rate of drug elimination depends on the contribution of the renal route to total elimination as well as on the polarity of the un-ionized form and the degree of ionization of the molecule. This energy-dependent process may be blocked by metabolic inhibitors. Anions and cations are handled by separate transport mechanisms. Normally, the anion secretory system eliminates metabolites conjugated with glycine, sulfate, or glucuronic acid.
Anionic compounds compete with one another for secretion.
Organic cations compete with each other but usually not with anions. Biliary Excretion Drugs and their metabolites that are extensively excreted in bile are transported across the biliary epithelium against a concentration gradient, requiring active secretory transport. Conjugation, particularly with glucuronic acid, also leads to biliary excretion. In the enterohepatic cycle, a drug secreted in bile is reabsorbed from the intestine. Drug conjugates secreted into the intestine also undergo enterohepatic cycling when they are hydrolyzed and the drug is reabsorbed.