Tubular reabsorption, a process occurring post-glomerular filtration of drugs in the renal tubule, is a critical determinant of drug half-life. 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. This process can either be active, commonly seen with endogenous substances like electrolytes and glucose, or passive, typical for many exogenous substances, including drugs. Active reabsorption is rare among drugs, with oxopurinol (a metabolite of allopurinol) being one of the few examples. Passive reabsorption is driven by concentration gradients established by back diffusion or reabsorption of water along with sodium and other inorganic ions.

Most drugs are weak acids or bases; their ionization level depends 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 an overdose of weakly acidic drugs, such as phenobarbital, 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.