Premium
Lamotrigine pharmacokinetics following oral and stable‐labeled intravenous administration in young and elderly adult epilepsy patients: Effect of age
Author(s) -
Polepally Akshanth R.,
Brundage Richard C.,
Remmel Rory P.,
Leppik Ilo E.,
Pennell Page B.,
White James R.,
Ramsay R. Eugene,
Kistner Brett M.,
Birnbaum Angela K.
Publication year - 2018
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.14519
Subject(s) - pharmacokinetics , medicine , nonmem , lamotrigine , bioavailability , dose , epilepsy , population , oral administration , anesthesia , pharmacology , environmental health , psychiatry
Summary 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.