3.20: Drug Elimination by Renal Route: Tubular Reabsorption

During the process of renal excretion, as the glomerular filtrate progresses to the distal convoluted tubule (DCT), drugs that are highly permeable, lipophilic, and nonionized undergo passive reabsorption from the tubular fluid into the surrounding peritubular capillaries. This reabsorption process restricts their elimination through the kidneys. However, the majority of drugs are either weak acids or weak bases, and their ionization level is dependent on pH. By altering the pH of urine, the reabsorption of these drugs can be hindered. When urine becomes alkaline, weak acidic drugs become predominantly ionized. Due to the decreased permeability of ionized forms through tubular cells, these drugs remain in the lumen and are ultimately expelled in the urine. This mechanism, known as 'ion trapping,' prevents reabsorption and enhances renal clearance of unwanted drugs. For example, in cases of phenobarbital overdose—a weak acid—treatment with bicarbonate is used to alkalinize the urine. This action ionizes the drug, impeding its back diffusion. Similarly, when dealing with an overdose of weakly basic drugs such as amphetamines, urine acidification is employed to ensure the ionized drug is not reabsorbed.

During renal excretion, as the glomerular filtrate reaches the DCT, highly permeable lipophilic and nonionized drugs are passively reabsorbed from the tubular fluid into the peritubular capillaries. This tubular reabsorption limits their renal excretion.

Most drugs, however, are weak acids or weak bases, and the extent of their ionization is pH dependent. By manipulating the pH of the urine, reabsorption of such drugs can be prevented.

When the urine is made alkaline, weakly acidic drugs are largely ionized. As the ionized forms are less permeable through the tubular cells, they are retained in the lumen and eventually excreted in the urine. This process of 'ion trapping' prevents reabsorption and increases renal clearance of undesirable drugs.

For instance, an overdose of phenobarbital —a weak acid—is treated with bicarbonate which makes the urine alkaline. This ionizes the drug and prevents its back diffusion.

Similarly, an overdose of weakly basic amphetamines, is treated by acidifying the urine such that the ionized drug does not get reabsorbed.