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

Effect of age

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 1 2018

Fingerprint

Intravenous Administration
Young Adult
Epilepsy
Pharmacokinetics
Biological Availability
lamotrigine
Liver Diseases
Heart Diseases
Spectrum Analysis
Gases
Body Weight
Kidney

Keywords

  • antiseizure drug
  • elderly
  • epilepsy
  • pharmacokinetics

PubMed: MeSH publication types

  • Journal Article
  • Multicenter Study
  • Research Support, N.I.H., Extramural

Cite this

Lamotrigine pharmacokinetics following oral and stable-labeled intravenous administration in young and elderly adult epilepsy patients : Effect of age. / Polepally, Akshanth R.; Brundage, Richard; Remmel, Rory P; Leppik, Ilo E; Pennell, Page B.; White, James R.; Ramsay, R. Eugene; Kistner, Brett M.; Birnbaum, Angela K.

In: Epilepsia, Vol. 59, No. 9, 01.09.2018, p. 1718-1726.

Research output: Contribution to journalArticle

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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.",
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AU - Brundage, Richard

AU - Remmel, Rory P

AU - Leppik, Ilo E

AU - Pennell, Page B.

AU - White, James R.

AU - Ramsay, R. Eugene

AU - Kistner, Brett M.

AU - Birnbaum, Angela K

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AB - 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.

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