Correlation of levetiracetam concentration in peripheral blood mononuclear cells with clinical efficacy: A sensitive monitoring biomarker in patients with epilepsy.
Seizure
; 78: 71-77, 2020 May.
Article
en En
| MEDLINE
| ID: mdl-32213443
PURPOSE: Therapeutic drug monitoring (TDM) is increasingly recommended in antiepileptic drug (AED) therapy, yet a complex relationship exists between the unbound-drug serum concentration (Cu.serum) as a monitoring biomarker and clinical efficacy. The study was designed to investigate the validity of the intracellular unbound-drug concentration in Peripheral Blood Mononuclear Cells (Cu.PBMC) as a feasible TDM tool in relation to levetiracetam (LEV). METHODS: Patients from epilepsy out-patient centre were included in a 4-month descriptive prospective study. Trough serum and PBMC LEV concentrations were monthly determined using HPLC and correlated with clinical features, demographic data, and P-glycoprotein (P-gp) expression. RESULTS: Seventy-patients completed the study with a LEV dose range of 500-3000 mg/day. An absolute range for LEV Cu.serum and Cu.PBMC was 1.00-26.99 and 0.33-4.43 µg/mL, respectively. Unlike Cu.serum, the average four-month LEV Cu.PBMC displayed a significant positive correlation with clinical features and P-gp expression; where patients with higher LEV Cu.PBMC experienced less number of seizure/month, better cognition and quality of life, and had a more reduction in P-gp expression, but no significant correlation with LEV daily dose was observed. A therapeutic response threshold of ≥ 0.82 µg/mL for LEV Cu.PBMCwas perceived by using a receiver operating characteristic curve that related the number of seizure/month to the LEV Cu.PBMC. The validity of this therapeutic threshold was significant in contrast to LEV Cu.serum. CONCLUSION: Levetiracetam PBMC concentration is a more sensitive biomarker for LEV efficacy and correlates better with clinical events than Cu.serum and could represent a novel tool for more precise LEV monitoring.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Leucocitos Mononucleares
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Monitoreo de Drogas
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP
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Epilepsia
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Levetiracetam
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Anticonvulsivantes
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
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Observational_studies
Límite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Seizure
Asunto de la revista:
NEUROLOGIA
Año:
2020
Tipo del documento:
Article