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Abstract
Background: Fampridine (4-aminopyridine) is a potassium channel blocker that has been evaluated
as a treatment for patients with spinal cord injury and multiple sclerosis.
Objective: The purpose of this study was to determine the pharmacokinetics of a single dose
of an orally administered solution of 14C-labeled fampridine in healthy volunteers.
Methods: In this open-label, single-dose study conducted in an inpatient setting, healthy
adult men were administered an oral solution containing 15 mg of 14C-labeled fampridine (100 μCi) in a fasted state. In addition to blood sampling for
analysis of plasma 14C-radioactivity at prescribed intervals over 7 days, all urine and feces were collected
for analysis of drug recovery and disposition. Urine samples were also analyzed for
metabolic profiling. Plasma pharmacokinetic parameters of the 14C-radiolabeled drug were determined using standard liquid-scintillation techniques.
Recovery was calculated to provide the total amount of radioactivity excreted as a
proportion of the original dose. Nonhydrolyzed and hydrolyzed urine extracts were
analyzed for radioactivity and metabolites using reverse-phase, isocratic high-performance
liquid chromatography with spectrophotometric and radioactive detection. Tolerability
was assessed through evaluation of vital signs, hematologic and other laboratory parameters,
and electrocardiography.
Results: The 4 white male subjects had a mean (SD) age of 21 (2) years. No clinically significant
abnormalities in vital signs, clinical chemistry, hematology, urinalysis, or electrocardiography
were observed either before or during the study. Peak plasma radioactivity was reached
at 1 hour after dosing, with a median concentration of 72.9 ng · mL−1. There was complete disappearance of radioactivity by 24 hours (limit of quantitation,
400 disintegrations/min per peak), and the calculated median t1/2 was 3.14 hours. Total cumulative recovery of 14C-radioactivity was 96.36%, with only 0.51% of drug recovered in feces. On chromatography,
2 metabolites accounted for a low proportion of total urinary radioactivity (3% and
6% of total radioactivity in the interval from 0 to 4 hours after dosing; 17% and
9% in the interval from 8 to 12 hours after dosing). Three subjects reported mild
and transient dizziness occurring 1 half-hour after dosing; this was considered possibly
related to the study drug.
Conclusion: Fampridine administered as an oral solution was rapidly absorbed and was nearly completely
and rapidly eliminated as unchanged drug via urinary excretion, suggesting that it
is unlikely to undergo substantial metabolic transformation.
Key words:
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Article info
Publication history
Accepted:
January 26,
2009
Identification
Copyright
© 2009 Excerpta Medica Inc. All rights reserved. Published by Elsevier Inc.
