Lamotrigine pharmacokinetics following oral and stable-labeled intravenous administration in young and elderly adult epilepsy patients: Effect of age

Akshanth R. Polepally, Richard C. Brundage, Rory P. Remmel, Ilo E. Leppik, Page B. Pennell, James R. White, R. Eugene Ramsay, Brett M. Kistner, Angela K. Birnbaum

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3 Scopus citations

Abstract

Objective: The objectives of this study were to investigate the effect of age on pharmacokinetic parameters of lamotrigine (LTG) and estimate parameter variability. Methods: Patients (>18 years old) who were already on a steady-state dose of LTG therapy with no interacting comedications were enrolled. Patients with significant cardiac disease, severe kidney dysfunction, or moderate-to-severe liver dysfunction were excluded. Fifty milligrams of a stable-labeled intravenous LTG formulation (SL-LTG) replaced 50 mg of a patient's normal daily oral LTG dose. Thirteen blood samples were collected in each person over 96 hours. SL-LTG and unlabeled LTG concentrations were measured simultaneously by gas chromatography–mass spectrometry. Concentration-time data were analyzed by nonlinear mixed-effects modeling (NONMEM version 7.3). Results: Twenty-eight patients representing 16 young (18-48 years old) and 12 elderly (63-87 years old) patients were included, yielding 382 unlabeled and 351 SL-LTG concentrations. A two-compartment model with first-order absorption and elimination adequately described the plasma concentration-time data. Bioavailability of oral LTG was approximately 74% and did not differ by age. LTG clearance was 27.2% lower in elderly than in young patients (1.80 L/h for a 70-kg patient). Significance: Although LTG bioavailability was not affected by age, LTG clearance was 27.2% lower in elderly versus young patients of comparable body weight, possibly indicating lower dosages being needed in this population.

Original languageEnglish (US)
Pages (from-to)1718-1726
Number of pages9
JournalEpilepsia
Volume59
Issue number9
DOIs
StatePublished - Sep 2018

Bibliographical note

Funding Information:
This study was supported by the following grants: National Institute of Health - National Institute of Neurological Disorders and Stroke P50 16308, National Center for Research Resources (NCRR) M01‐RR00400, NCRR M01‐ RR16587, and NCRR M01‐RR00039.

Keywords

  • antiseizure drug
  • elderly
  • epilepsy
  • pharmacokinetics

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