Population Pharmacokinetics of Eslicarbazepine Acetate in Patients With Partial-onset Seizures

Authors: Kharidia J, Versavel M, Lu Q, Zummo J, Ludwig E, Grasela TH, Fiedler-Kelly J, Maier G, Soares-da-Silva P
Conference: ASCPT
Keywords: 1-compartment, AED, allometric scaling, Carbamazepine, central nervous system agents, clearance, esli, neurology, once daily, Phase 3, phenobarbital, QD, Sunovion, valproate, volume of distribution
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Instruction

  • Eslicarbazepine acetate (ESL) is a novel once-daily antiepileptic drug (AED) currently under clinical development in the US.
  • Following oral administration, ESL is rapidly and extensively metabolized to eslicarbazepine, which represents about 95% of total systemic drug exposure.
  • Maximum plasma concentration (Cmax) of eslicarbazepine is attained approximately 3 hours post-dose, with steady state attained after 4 to 5 days of once-daily (QD) dosing.
  • Eslicarbazepine is eliminated from the systemic circulation, primarily by renal excretion, in the unchanged and glucuronide conjugate forms.
  • Population pharmacokinetic (PK) modeling was undertaken to describe the PK of the eslicarbazepine analyte in the clinically relevant patient population, and provide a means to support a later exposure-response evaluation of eslicarbazepine efficacy endpoints.

American Society for Clinical Pharmacology and Therapeutics (ASCPT), Dallas, Texas, March 2011

By Jahnavi Kharidia, Mark Versavel; Qiang Lu, Jacqueline Zummo; Elizabeth Ludwig, Thaddeus H. Grasela, Jill Fiedler-Kelly, Gary Maier, Patricio Soares-da-Silva