Therapeutic Drug Monitoring and Model-Informed Precision Dosing of Oral TKIs and PARP Inhibitors: A Practical Framework for Clinical Implementation - PubMed
6 hours ago
- #precision dosing
- #therapeutic drug monitoring
- #oncology
- Oral TKIs and PARP inhibitors are given at fixed doses but have high pharmacokinetic variability, leading to inconsistent exposure and outcomes.
- Therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD) help tailor doses to optimize efficacy and reduce toxicity in oncology.
- Strong evidence supports TDM for imatinib and sunitinib to improve clinical results by achieving target trough concentrations.
- Alectinib, cabozantinib, trametinib, and lenvatinib have exposure-response links and thresholds suitable for selective TDM use.
- For osimertinib, brigatinib, olaparib, and niraparib, TDM is more relevant for managing toxicity rather than boosting efficacy.
- Lorlatinib lacks a clear therapeutic window, limiting routine TDM application.
- Steady-state trough concentration is the preferred sampling method, used in cases like disease progression, severe side effects, drug interactions, or adherence issues.
- MIPD combines patient-specific factors with pharmacokinetic models to design personalized dosing plans.
- TDM and MIPD are ready for clinical adoption in some oral targeted therapies, with further trials needed to refine exposure targets and expand evidence-based practices.