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Single‐Dose Pharmacokinetics of Sustained‐Release Fampridine (Fampridine‐SR) in Healthy Volunteers and Adults With Renal Impairment
Author(s) -
Smith William,
Swan Suzanne,
Marbury Thomas,
Henney Herbert
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009344857
Subject(s) - pharmacokinetics , medicine , multiple sclerosis , renal function , confidence interval , urology , creatinine , psychiatry
Fampridine‐SR is a sustained‐release formulation of fampridine (4‐aminopyridine), a potassium channel blocker demonstrated to improve walking ability in patients with multiple sclerosis. This study evaluated the pharmacokinetics of fampridine and its metabolites after administration of fampridine‐SR 10 mg in healthy volunteers and in subjects with mild, moderate, or severe renal impairment (5 per group). Analysis of variance was used to calculate 90% confidence intervals (CIs) for the ratios (impaired/healthy) of least squares mean in maximum plasma concentration (C max ) and area under the plasma concentration‐time curve (AUC). Clearance was primarily through urinary excretion. In renally impaired subjects, fampridine plasma concentrations were consistently higher than in healthy individuals: ratios for C max ranged from 166.5% to 199.9% for mild and severe renal impairment, respectively. AUC 0–∞ ratios ranged from 175.3% to 398.7%, respectively, for mild and severe renal impairment. Mean terminal disposition half‐life was 6.4 hours in healthy individuals, compared with 7.4, 8.1, and 14.3 hours in patients with mild, moderate, and severe renal impairment, respectively. Regression analysis confirmed the significant relationship between creatinine clearance and extent of exposure as quantified by AUC for fampridine and its metabolites, suggesting cautious use in patients with mild renal impairment and avoidance in cases of moderate or severe renal impairment.