Abstract Details

Title Population Pharmacokinetics Of Levetiracetam In Mexican Adult Patients With Epilepsy

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P11 - Poster Session 11 (8:00 AM-9:00 AM)

Poster/Presentation
Number 12-012

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<6.63). Final model equations were: Ka(h^-1)=3.63, V/F(L)=29.7*(BSA/1.68)^2.85 and CL/F(L/h)=2.79*(CrCL)/96.2)^0.588. Inter-individual variability associated to V/F and CL/F decreased from 45.8% and 52.3% in the base model to 30.4% and 43.6%, respectively, in the final model. A priori estimation allowed proposing dosing recommendations to reach target trough concentrations (12–46 µg/mL), and a posteriori estimation based on Bayesian approach showed enhanced predictive performance. Dosing simulations support 1000 mg 12-hourly dosing of levetiracetam for patients with normal renal function (CrCL~60mL/min) with higher dose needed for higher values (1500 mg 12-hourly for CrCL~100mL/min).

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.

Authors/Disclosures
Maria Patricia Hernández Mitre, PhD PRESENTER	No disclosure on file
	No disclosure on file
Ildefonso Rodriguez-Leyva, MD, PhD, FAAN (Facultad de Medicina, Universidad Autonoma de San Luis Potosi)	Dr. Rodriguez-Leyva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Rodriguez-Leyva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Laboratorios Columbia.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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