Population Pharmacokinetics Of Levetiracetam In Mexican Adult Patients With Epilepsy

Objective: To develop and validate a population pharmacokinetic model of levetiracetam in Mexican adult patients with epilepsy to propose individualized dosing regimens. Background: Levetiracetam is an antiepileptic drug used to treat all types of seizures in patients of all ages. Therapeutic drug monitoring (TDM) may be beneficial to maintain an individual therapeutic range in patients where the pharmacokinetics of levetiracetam may be altered, such as elderly patients. Design/Methods: Protocol approved by the Hospital’s Research Ethics Committee. The study included 367 plasma samples between 15 minutes and 12 hours post-dose from 107 adults receiving oral levetiracetam in monotherapy or in combination therapy with other antiepileptic drugs. Pharmacokinetic data, as well as patient demographic, clinical characteristics, other drug therapy, and the use of innovator or generic products of levetiracetam were collected. Samples were analyzed by a validated HPLC-UV method. Population modelling and dosing simulations were performed with NONMEM. Internal validation was executed by bootstrap and Visual Predictive Check. Results: The pharmacokinetics of levetiracetam was described by a one-compartment model with first-order absorption and linear elimination. Covariates model was selected through stepwise forward inclusion (ΔOFV>3.84) and backward deletion (ΔOFV Conclusions: A population pharmacokinetic model of levetiracetam in Mexican adult patients with epilepsy was developed. Dosing regimens should be personalized to the patient’s creatinine clearance. Disclosure: Dr. Hernandez Mitre has nothing to disclose. Dr. Medellin Garibay has nothing to disclose. Dr. Rodriguez-Leyva has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Teva, UCB. Dr. Castillo-Ibarra has nothing to disclose. Dr. Rodriguez Pinal has nothing to disclose. Dr. Zarazua Guzman has nothing to disclose. Dr. Jung Cook has nothing to disclose. Dr. Romano Moreno has nothing to disclose. Dr. Milan Segovia has nothing to disclose.