High Anti-Tumour Necrosis Factor Trough Concentrations--Only a Cost Issue or Also Hidden Dangers Ahead?

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...

The therapeutic index of a drug is a key parameter in pharmacology that quantifies the relative safety of a drug by calculating the ratio between the dose that causes toxicity in half the population (50%) to the dose that proves to be effective for half the population (50%). It provides a spectrum of doses for a particular drug ranging from effective to potentially toxic. To illustrate, consider an anticoagulant agent like warfarin. It possesses a narrow window within its therapeutic index to...

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.

Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood at designated intervals to ensure the drug concentration stays within a therapeutic range. This monitoring is crucial for optimizing individual dosage regimens, enhancing therapeutic efficacy, and minimizing drug-related toxicity. TDM is vital for drugs with narrow therapeutic windows, significant variability in pharmacokinetics, and a clear correlation between plasma levels and...

Upon entering the systemic circulation, drugs can distribute into the interstitial and intracellular fluid of various tissue cells. This distribution is facilitated by the binding of drugs to different cellular components within tissues, which may lead to drug accumulation in specific areas. Drugs bound to tissue components serve as reservoirs that release free drugs back into the system, prolonging the drug's overall action. However, this accumulation can also result in local toxicity.
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Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...