Cis-platinum and distal renal tubule toxicity

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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...
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The renal tubule is divided into three parts: the proximal convoluted tubule (PCT), the Loop of Henle (LOH), and the distal convoluted tubule (DCT).
Proximal Convoluted Tubule (PCT):
The PCT is the initial segment of the renal tubule, extending from the Bowman's capsule that encloses the glomerulus. Its convoluted structure and microvilli-lined cells increase the surface area for reabsorption. The PCT reabsorbs glucose, amino acids, sodium, and water from the filtrate, ensuring essential...
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Renal Drug Excretion: Tubular Reabsorption

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...
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Active tubular secretion is a robust, energy-demanding process that utilizes carrier systems to transport drugs into renal tubules. The active renal secretion systems include the organic anion transporter (OAT) for weak acids and the organic cation transporter (OCT) for weak bases. Structurally similar drugs can compete for the same transporter, potentially leading to drug accumulation and toxicity. However, this principle can be exploited therapeutically. One example is probenecid (Probalan),...
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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...
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