Editorial comment: tenofovir nephrotoxicity--the disconnect between clinical trials and real-world practice

Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.

In patients with renal disease, dosage adjustments are necessary to maintain therapeutic plasma drug concentrations and prevent toxicity or subtherapeutic exposure. Renal impairment alters drug pharmacokinetics, especially in conditions like uremia, where changes such as prolonged elimination half-life and altered apparent volume of distribution can significantly affect drug disposition. These changes require careful modification of the dosing regimen to achieve the desired clinical...

As primary excretory organs, the kidneys maintain homeostasis by removing waste substances from the bloodstream. They comprise over a million units called nephrons, which serve as the kidney's functional units.
A nephron consists of two primary structures: the renal corpuscle and the renal tubule. The renal corpuscle contains the glomerulus, a network of capillaries where the first step of renal excretion, glomerular filtration, occurs. Blood pressure forces water, ions, and small molecules out...

Renal clearance is a crucial parameter in pharmacokinetics that quantifies the rate at which the kidneys excrete a drug. It represents a constant fraction of the central volume of distribution containing the drug that the kidney eliminates per unit of time.
Renal clearance can be calculated using different methods. One approach is to divide the urinary drug excretion rate by the plasma drug concentration. This method directly measures renal clearance, indicating the kidneys' efficiency in...

In patients with renal impairment, drugs undergo significant changes in their pharmacokinetics, which require dosage adjustments to ensure safe and effective therapy.
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...

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...