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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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Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
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Dosage Regimens: Partial Pharmacokinetic Parameters01:01

Dosage Regimens: Partial Pharmacokinetic Parameters

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It is not uncommon for complete drug pharmacokinetic profiles to remain elusive in pharmacokinetics. This necessitates certain educated assumptions by pharmacokineticists to determine appropriate dosage regimens without comprehensive pharmacokinetic data from animal or human studies. One prevalent assumption is setting the bioavailability factor, denoted as F, to 1 or 100%. This assumption caters to the scenario where a drug doesn't achieve full systemic absorption, resulting in the patient...
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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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A drug interaction occurs when the concurrent use of another drug, food, or an external substance alters the pharmacological activity of a drug. This interaction can modify the action of the original drug, affecting its effectiveness and safety.Drug–food interactions are significant as they impact drug absorption, metabolism, and excretion. For example, grapefruit juice is a well-known disruptor of drug metabolism. It inhibits the cytochrome P450 3A4 enzyme, crucial for the metabolism of...
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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...
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Decrease in voriconazole concentration-to-dose ratio after letermovir initiation: a retrospective, observational

Shinichi Hikasa1, Shota Shimabukuro2, Yuko Osugi3

  • 1Department of Pharmacy, Hyogo College of Medicine College Hospital, Hyogo, 663-8501, Japan. ykhikasa@hyo-med.ac.jp.

Bone Marrow Transplantation
|October 26, 2020
PubMed
Summary
This summary is machine-generated.

Letermovir coadministration significantly alters voriconazole levels in hematopoietic stem cell transplant (HSCT) recipients. Frequent therapeutic drug monitoring of voriconazole is crucial for HSCT patients receiving letermovir.

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Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Hematology

Background:

  • Letermovir is a key agent for preventing cytomegalovirus (CMV) infection in hematopoietic stem cell transplantation (HSCT) recipients.
  • Voriconazole exposure is reduced by letermovir in healthy individuals, but its impact on HSCT recipients is not well understood.
  • Understanding drug interactions is vital for optimizing treatment outcomes in immunocompromised patients.

Purpose of the Study:

  • To investigate the effect of letermovir coadministration on voriconazole concentrations in HSCT recipients.
  • To evaluate changes in the voriconazole concentration-to-dose ratio during different post-transplant periods.

Main Methods:

  • Retrospective, observational, single-center study from January 2016 to July 2019.
  • Analyzed 42 HSCT recipients receiving voriconazole, divided into letermovir (n=15) and control (n=27) groups.
  • Measured voriconazole concentration-to-dose ratio during three periods: pre-HSCT (days -7 to -1), early post-HSCT (days 4-10), and later post-HSCT (days 11-17).

Main Results:

  • The letermovir group showed a significantly lower percent change (-33.2%, p<0.05) in the voriconazole concentration-to-dose ratio from period A to C compared to the control group.
  • This indicates a notable alteration in voriconazole pharmacokinetics when coadministered with letermovir in HSCT recipients.
  • The findings highlight a potential for sub-therapeutic or supra-therapeutic voriconazole levels without monitoring.

Conclusions:

  • Coadministration of letermovir significantly impacts voriconazole concentrations in HSCT recipients.
  • Frequent therapeutic drug monitoring of voriconazole is essential in HSCT patients receiving letermovir.
  • Regular dose adjustments based on therapeutic drug monitoring are recommended to ensure optimal voriconazole efficacy and safety.