Toward individualized precision dosing of perampanel: Integrating therapeutic drug monitoring, drug-drug interactions, and pharmacogenetics.

Metabolism by CYP3A4/CYP3A5, highly sensitive to enzyme inducers; the CYP3A5*3 polymorphism is proposed as a stratification criterion for initial dose selection.

This article proposes an individualised dosing strategy for perampanel, a highly selective non-competitive AMPA receptor antagonist used in drug-resistant epilepsy, whose interindividual pharmacokinetic and pharmacodynamic variability is marked and whose efficacy and adverse effects (dizziness, neuropsychiatric disturbances) are strongly concentration-dependent. The strategy combines three dimensions: therapeutic drug monitoring as the core tool for defining a patient-specific target concentration, proactive management of CYP3A4/CYP3A5-mediated drug-drug interactions — particularly the reduced exposure caused by potent enzyme inducers — and integration of pharmacogenetic information, including the CYP3A5*3 polymorphism, to refine initial dose selection. The authors highlight the value of this approach for vulnerable populations: children, pregnant women and patients with renal impairment.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The proposed framework is coherent and reflects real practice, where perampanel dosing is mostly driven by tolerability and enzyme-inducing co-medications. But this is a review and proposal, with no prospective validation and no cohort: the actual role of CYP3A5 genotype in initial dose selection is not demonstrated, and the pharmacogenetic component remains secondary to therapeutic drug monitoring and drug interactions. Worth reading as a roadmap to be tested, not as a dosing recommendation.

Analysis by Dr Thibaut Benquey