6.7 : Renal Drug Excretion: Effect of Urine pH, Flow Rate, and Drug pKa

The pH of urine, the drug's pK_a, and the urine flow rate are vital parameters for drug reabsorption and excretion. Urinary pH varies between 4.6 and 8.0 and is influenced by diet, drug intake, and the patient's pathophysiology. It affects a drug's ionization state and reabsorption. For instance, carbohydrate-rich food produces alkaline urine promoting drug excretion, while proteins and certain medications like ascorbic acid lead to acidic urine enhancing reabsorption.

The pK_a of a drug, dictating its ionization level at a specific pH, significantly impacts its reabsorption. Lipophilic substances are extensively reabsorbed, while polar molecules are not. Notably, the reabsorption of drugs with pK_a ranging from 3.0 to 8.0 (acidic) or 6.0 to 12.0 (basic) relies heavily on urine pH.

Lastly, urine flow rate also alters reabsorption. While pH-insensitive polar drugs remain unaffected, reabsorption is inversely related to urinary flow for weak acids and bases, which are pH-sensitive. Based on their reabsorption compared to water, drugs can be categorized into two: those with equal or greater reabsorption, like phenobarbital, exhibiting a linear relationship between renal clearance and excretion, and those with lesser reabsorption, such as theophylline, demonstrating a convex curvilinear relationship.

Strategies such as forced diuresis can be employed to enhance drug elimination in instances of toxicity or overdose. Understanding these parameters allows for better prediction of drug reabsorption and designing effective drug elimination strategies.