Lamotrigine pharmacokinetics following oral and stable-labeled intravenous administration in young and elderly adult epilepsy patients: Effect of age.
Epilepsia
; 59(9): 1718-1726, 2018 09.
Article
en En
| MEDLINE
| ID: mdl-30101556
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Epilepsia
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Lamotrigina
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Anticonvulsivantes
Tipo de estudio:
Clinical_trials
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Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Epilepsia
Año:
2018
Tipo del documento:
Article