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Therapeutic Drug Monitoring: Affecting Factors01:29

Therapeutic Drug Monitoring: Affecting Factors

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.
Factors Affecting Protein-Drug Binding: Patient-Related Factors01:29

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Protein-drug binding, a pivotal aspect of pharmacokinetics, is subject to considerable variability influenced by an array of patient-related factors. The intricate interplay of age, individual differences, and pathological conditions significantly impact the binding dynamics and subsequent pharmacological effects.
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Factors Affecting Drug Response: Overview01:21

Factors Affecting Drug Response: Overview

When it comes to infants and young children, they are typically administered smaller doses of medication in comparison to adults. This is primarily because their organ functions still need to fully develop, meaning their bodies are not as efficient at metabolizing or eliminating drugs. Additionally, their blood-brain barrier is more permeable than in adults. As a result, high concentrations of drugs can easily penetrate the central nervous system (CNS), potentially leading to neurological...
Factors Affecting Protein-Drug Binding: Drug-Related Factors01:18

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Drug binding to proteins is a complex phenomenon influenced by various drug-related factors, each playing a significant role in the interaction between drugs and proteins within the body.
One crucial factor in drug-protein binding is the drug's lipophilicity or its affinity for fat. More lipophilic drugs tend to have higher binding extents. For example, highly lipophilic drugs like cloxacillin exhibit substantial protein binding, with as much as 95% of the drug binding to proteins. In contrast,...
Factors Affecting Renal Clearance: Renal Impairment01:17

Factors Affecting Renal Clearance: Renal Impairment

Renal dysfunction significantly impairs the renal clearance of drugs, leading to potential complications in drug therapy. Renal failure, which can be caused by various factors, poses a significant challenge in the elimination of drugs from the body.
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Factors Affecting Protein-Drug Binding: Protein-Related Factors01:20

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Drug binding to proteins is a key aspect of pharmacokinetics and can influence a drug's distribution, absorption, and elimination in the body. Several factors, including the drug's physiochemical properties, protein concentration, disease states, and the number of binding sites on the protein, influence this process.
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Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay
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Published on: September 9, 2012

Recombinant factor concentrates may increase inhibitor development: a single centre cohort study.

T Strauss1, A Lubetsky, B Ravid

  • 1The Israeli National Hemophilia Center, Tel Hashomer Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.

Haemophilia : the Official Journal of the World Federation of Hemophilia
|February 9, 2011
PubMed
Summary

Early exposure to recombinant factor VIII (rFVIII) concentrates in haemophilia A (HA) patients may increase inhibitor risk. Continuous infusion treatments also showed a higher incidence of inhibitor development in this cohort.

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Area of Science:

  • Hematology
  • Immunology
  • Pediatrics

Background:

  • Inhibitor development is a significant concern in haemophilia A (HA) treatment.
  • Neonatal exposure to factor concentrates is common in Israel due to routine circumcision.
  • Recombinant factor VIII (rFVIII) products have been available since 1996.

Purpose of the Study:

  • To analyze the impact of early exposure and rFVIII administration on inhibitor occurrence in HA patients.
  • To investigate the influence of treatment regimens (bolus vs. continuous infusion) and family history on inhibitor development.

Main Methods:

  • Retrospective analysis of 292 pediatric HA patients with first symptomatic onset.
  • Follow-up for a median of 7 years to monitor inhibitor development against factor VIII.
  • Comparison of inhibitor rates between patients treated with rFVIII and Plasma Derived (PD) products, and analysis of treatment regimens.

Main Results:

  • 31/292 children (10.6%) developed high-titer inhibitors.
  • Inhibitor occurrence was significantly higher in neonatally rFVIII-exposed patients (32.5%) compared to PD-treated patients (8.8%).
  • Odds ratio for inhibitor formation in rFVIII-treated HA patients was 3.43; continuous infusion treatment also increased risk (P=0.025).

Conclusions:

  • Early exposure to recombinant factor concentrates may increase the risk of inhibitor formation in HA patients.
  • Continuous infusion regimens were associated with a higher risk of inhibitor detection.
  • Further prospective studies are needed to investigate the multiple variables affecting inhibitor incidence.