Clinical Application of Pharmacokinetics to Appraise Adherence to Levetiracetam in Portuguese Epileptic Patients

Abstract

Adherence to antiseizure drug treatment determines its effectiveness and safety, and consequently affects patients’ quality of life. Herein, we assessed adherence to levetiracetam in Portuguese patients with refractory epilepsy (n = 115), with resort to a pharmacokinetic drug monitoring approach. The pharmacokinetic parameters of levetiracetam in each patient were determined in steady-state while admitted to the hospital. Then, adherence was assessed by comparing the plasma concentration of the drug observed on the first day of hospitalization with the predicted plasma concentration, considering previously determined pharmacokinetic parameters. The rate of adherence was assessed according to gender, age, diagnosis, and antiseizure drug regimen. Among 115 enrolled patients, 49 (42.6%) were identified as non-adherent, 30 (26.1%) classified as under-consumers, and 19 (16.5%) as over-consumers. A relationship between adherence, daily dose and plasma concentrations was herein reported for the first time. Adherent patients received higher daily doses of levetiracetam [2500 (2000–3000) mg] than non-adherent over-consumers [1500 (1000–2000) mg] and non-adherent under-consumers [2000 (1500–3000) mg]. Higher average steady-state plasma concentrations of levetiracetam were found in non-adherent under-consumers [27.28 (15.33–36.36) mg/L], followed by adherent patients [22.05 (16.62–29.81) mg/L] and non-adherent over-consumers [17.50 (10.69–24.37) mg/L]. This study demonstrates that adherence (or lack thereof) influences the plasma concentrations of levetiracetam in steady-state and its pharmacological effects. Moreover, it emphasizes the importance of educating patients to encourage adherence to therapy. Otherwise, the risk of developing toxic and subtherapeutic concentrations is undeniable, compromising the therapeutic effect and safety of treatment.

The Importance of Drug Delivery in the Clinical Development and Lifecycle of Drug Products with Examples from Authorised Medicinal Products

“…Levetiracetam is an antiepileptic medication indicated as monotherapy in the treatment of partial onset seizures and as adjunct therapy in the treatment of partial onset seizures, monoclinic seizures, and primary generalised tonic-clonic seizures [50]. In a recent study by Silva et al [51], non-adherence to levetiracetam was reported as 42.6% among the study participants.…”

Initial therapeutic target attainment of perampanel in pediatric patients with epilepsy

“…Therapeutic drug monitoring (TDM) is an essential tool to address this complexity, enabling the definition of individual therapeutic concentrations and adaptive control of dosing to minimize drug interactions and prevent loss of efficacy or toxicity (Krasowski, 2010). Some studies have shown that PER plasma levels were affected by otherAEDs in routine TDM practice, including carbamazepine, phenobarbital, valproate and topiramate (Patsalos et al, 2016;Contin et al, 2018;Silva et al, 2023). A recent study indicated that enzyme-inductive AED could increase PER clearance (Fujita et al, 2022).…”