Abstract Details

Title Pharmaceutical Evaluation And Therapeutic Drug Monitoring Of Levetiracetam In Patients With Epilepsy

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 6-008

Objective Measure plasma concentrations of levetiracetam (LEV) in patients with epilepsy (PWE) under treatment with different LEV products, and assess pharmaceutical quality of innovative and generic LEV products.

Background Cost savings is the driving force for interchangeability of drugs, however, there is opposition to switching formulations of antiepileptic drugs (AEDs) because of concerns of inequivalence between innovative and generics. Therapeutic Drug Monitoring (TDM) allows to determine the impact of interchangeability of LEV products, as it may result in loss of seizure control or pharmacological toxicity.

Design/Methods Protocol approved by the Hospital’s Research Ethics Committee. Patients ≥18years were required to be under treatment with immediate-release LEV for 1week, in monotherapy or polytherapy with another AEDs. Each patient provided 1 to 4 samples of blood at different times in the range from 0 to 12h post-dose. Samples were analyzed by a validated HPLC-UV method. Pharmaceutical evaluation of innovative and 4 generics was tested as recommended by USP38/NF33-2015 Pharmacopeial Tests Procedures, which includes identification, assay, weight variation and dissolution.

Results

LEV plasma concentrations of 110 PWE were determined. Pharmacokinetic parameters Cmax=26.16µg/mL (500mg dose-normalized) and Tmax=1.37h were calculated using non-compartmental analysis with WinNonlin®. Median t_1/2 was 5.81h (5.1 to 6.7h) for patients ≤60years and 8.9h (7.74 to 10.92h) for elderly patients, which is greater due to age-associated decreased renal function. 53 (48.18%) patients present plasma concentrations within the therapeutic range (6 to 46µg/mL), and the rest might require dose adjustment. Only 10% of the patients acquire the innovative product. Linear correlation was found between reached Cmax and age (r=0.3816;p=0.0024), and body mass index (BMI) (r=-0.2939;p=0.0215). No correlation with different products administration (r=0.1326;p=0.3085). Tested products meet the acceptance criteria to all pharmacopeial procedures performed.

Conclusions

TDM of LEV in PWE has been successfully implemented and we demonstrated that tested generics are pharmaceutical equivalents to the innovative product of LEV.

Authors/Disclosures
PRESENTER	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
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