urinary pH effect

A drug molecule can wear two outfits: a neutral, fat-loving form that slips easily through cell membranes, and a charged form that does not. The acidity of the urine decides which outfit most of the drug wears at any moment, and that in turn decides whether the kidney can hold onto the drug or let it escape.

The chemistry follows the pH partition principle. A weakly acidic drug becomes more ionized, and therefore more trapped in alkaline urine, while a weakly basic drug becomes more ionized in acidic urine. Because only the uncharged form is reabsorbed across the tubule wall, conditions that increase ionization in the urine reduce reabsorption and increase excretion.

Clinicians use this deliberately in poisoning. Making the urine alkaline with sodium bicarbonate keeps a weak acid such as aspirin or phenobarbital ionized in the tubule, so it stays in the urine and is excreted faster. The trick only helps for drugs that are weak acids or bases handled appreciably by passive reabsorption; for strongly cleared or highly bound drugs it does little.