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Related Concept Videos

Renal Failure: Dose Adjustments01:11

Renal Failure: Dose Adjustments

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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...
434
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents01:29

Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents

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Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
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Therapeutic Drug Monitoring: Affecting Factors01:29

Therapeutic Drug Monitoring: Affecting Factors

200
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.
200
Drug Accumulation During Multiple Dosing: Intermittent IV Infusions01:24

Drug Accumulation During Multiple Dosing: Intermittent IV Infusions

232
Intermittent intravenous (IV) infusion is a method of drug administration where medications are delivered over short infusion periods followed by intervals of no drug delivery. This approach helps to prevent sustained high drug concentrations in the bloodstream, reducing the risk of adverse effects associated with prolonged exposure. Unlike continuous infusion, steady-state concentrations may not be achieved during a single dosing cycle but can be reached through repeated...
232
Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant01:25

Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant

207
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...
207
Acute Kidney Injury IV: Diagnostic Studies and Prevention01:30

Acute Kidney Injury IV: Diagnostic Studies and Prevention

257
Accurate diagnosis and effective prevention are critical in managing Acute Kidney Injury (AKI), which is linked to high mortality rates ranging from 10% to 80%. Timely recognition of at-risk patients and careful monitoring can significantly reduce the likelihood of kidney damage.Diagnostic Assessments:The diagnostic process starts with a comprehensive medical history to identify prerenal, intrarenal, and postrenal causes.Prerenal causes, such as dehydration, hypotension, or blood loss, should...
257

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High-Dose Methotrexate Nephrotoxicity.

Jaya Kala1, Scott C Howard2,3,4

  • 1Division of Nephrology, Department of Internal Medicine, University of Texas Health Science Center-McGovern Medical School, Houston, Texas, USA, jaya.kala@uth.tmc.edu.

American Journal of Nephrology
|October 24, 2025
PubMed
Summary
This summary is machine-generated.

High-dose methotrexate (HDMTX) can cause kidney injury. Prompt recognition and management of delayed elimination and renal dysfunction are crucial for preventing severe toxicities and improving patient outcomes.

Keywords:
Acute kidney injuryChemotherapyHigh-dose methotrexateLeucovoringlucarpidase

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Area of Science:

  • Oncology
  • Pharmacology
  • Nephrology

Background:

  • Methotrexate (MTX) is an antimetabolite anticancer agent used at various doses.
  • High-dose methotrexate (HDMTX), >500 mg/m2, treats various cancers including leukemia and osteosarcoma.
  • Renal toxicity occurs in 2%-39% of HDMTX courses, with severe cases around 2%.

Purpose of the Study:

  • To emphasize the importance of MTX pharmacokinetics and pharmacodynamics.
  • To highlight cellular mechanisms of MTX anticancer activity.
  • To review MTX-induced renal injury pathophysiology and management strategies.

Main Methods:

  • Review of literature on MTX pharmacokinetics, pharmacodynamics, and toxicity.
  • Analysis of cellular mechanisms of MTX.
  • Exploration of prevention and management strategies for MTX nephrotoxicity.

Main Results:

  • Delayed MTX elimination and renal dysfunction can lead to severe toxicities.
  • Increased hydration, high-dose leucovorin, and glucarpidase are key treatments.
  • Effective management of toxicities improves cancer prognosis and survival.

Conclusions:

  • Understanding MTX pharmacokinetics and pharmacodynamics is vital.
  • Prompt recognition and treatment of MTX toxicities are crucial.
  • Effective management strategies enhance patient outcomes and survival.