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Therapeutic Drug Monitoring: Affecting Factors01:29

Therapeutic Drug Monitoring: Affecting Factors

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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.
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Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant01:25

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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...
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Preoperative ManagementThe primary goals of preoperative management in kidney transplantation are to optimize the patient’s metabolic state and prepare them for surgery through diet adjustments, necessary dialysis, and tailored medical treatment. This phase also involves comprehensive infection screening and patient education about the surgical procedure and postoperative care to improve outcomes and adherence.Medical ManagementA comprehensive evaluation is required for both the living...
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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...
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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.
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Methotrexate nephrotoxicity: a pragmatic approach.

Yara Mouawad1, Jaya Kala

  • 1Division of Renal Diseases and Hypertension, Department of Internal Medicine, University of Texas Health Science Center-McGovern Medical School, Houston, Texas, USA.

Current Opinion in Nephrology and Hypertension
|December 8, 2025
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Summary

Managing high-dose methotrexate (HDMTX) toxicity requires personalized strategies. Emerging risk factors and advanced monitoring, including pharmacogenomics and pharmacokinetic modeling, are key to reducing renal impairment and delayed methotrexate elimination (DME).

Keywords:
acute kidney injurydelayed methotrexate eliminationglucarpidasehigh-dose methotrexate

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Area of Science:

  • Oncology
  • Pharmacology
  • Nephrology

Background:

  • High-dose methotrexate (HDMTX) is crucial for treating various cancers.
  • Preventive measures for HDMTX toxicity frequently fail, leading to renal impairment and delayed methotrexate elimination (DME), increasing systemic toxicity risk.

Purpose of the Study:

  • To review existing, current, and novel strategies for managing HDMTX-related toxicity.
  • To highlight advancements in understanding and mitigating HDMTX-induced renal complications.

Main Methods:

  • Literature review of past, current, and emerging management strategies for HDMTX toxicity.
  • Analysis of recent research on risk factors, nephroprotective agents, and monitoring tools.

Main Results:

  • Host genetic factors, hypoalbuminemia, and body surface area are identified as DME contributors.
  • Investigated nephroprotective agents include synthetic oxadiazole (5b), empagliflozin, and amlodipine.
  • Glucarpidase shows improved outcomes and renal recovery; early therapeutic drug monitoring predicts kidney injury; MTXPK.org aids DME management.

Conclusions:

  • Personalized therapeutic strategies are essential for reducing renal toxicity and DME.
  • Advances in pharmacogenomics, risk factor identification, and pharmacokinetic modeling are critical.
  • Timely methotrexate monitoring and patient-specific modeling improve treatment outcomes.