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Brivaracetam disposition in renal impairment
Maria Laura Sargentini-Maier1, Antoni Sokalski, Pierre Boulanger
1UCB Pharma, Chemin du Foriest, B-1420 Braine-l'Alleud, Belgium.
Journal of Clinical Pharmacology
|January 12, 2012
Summary
Brivaracetam disposition was studied in patients with severe renal impairment. Despite increased metabolite exposure, dose adjustments are likely unnecessary for epilepsy treatment.
Area of Science:
- Pharmacology
- Nephrology
- Clinical Pharmacy
Background:
- Brivaracetam is an antiepileptic drug targeting SV2A.
- Renal impairment can alter drug pharmacokinetics.
- Understanding brivaracetam's behavior in renal dysfunction is crucial.
Purpose of the Study:
- To characterize the pharmacokinetic disposition of brivaracetam and its metabolites in patients with severe renal impairment.
- To compare brivaracetam exposure and clearance in renally impaired patients versus healthy controls.
Main Methods:
- Single oral dose (200 mg) of brivaracetam administered to 9 patients with severe renal impairment and 9 healthy controls.
- Plasma and urine concentrations of brivaracetam and 3 inactive metabolites measured up to 72 hours.
- Noncompartmental pharmacokinetic analysis performed.
Main Results:
- Brivaracetam Cmax was unchanged; AUC was slightly increased (1.21-fold) in renal impairment.
- Renal and nonrenal clearance of brivaracetam decreased.
- Exposure to brivaracetam metabolites (acid, hydroxy, hydroxyacid) increased significantly (AUC: 3.2- to 21.5-fold).
- Metabolite renal clearance decreased 10-fold.
Conclusions:
- Increased metabolite exposure in renal impairment did not raise safety concerns based on toxicology studies.
- Brivaracetam dose adjustment is likely not required in patients with renal dysfunction.
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