Pharmacokinetics of an immediate-release oral formulation of Fampridine (4-aminopyridine) in normal subjects and patients with spinal cord injury.
Plasma concentration profiles of the K+ channel-blocking compound Fampridine were obtained from (1) control subjects (n = 6) following oral administration of doses of 10, 15, 20, and 25 mg and (2) patients with spinal cord injury (SCI) (n = 11) following a single oral dose of 10 mg of an immediate-release formulation. Plasma concentrations were determined using a reversed-phase ion-pair high-performance liquid chromatography (HPLC) assay with ultraviolet light detection employing liquid extraction. The drug was rapidly absorbed with a tmax approximately 1 hour for both groups; tmax was independent of dose. Cmax and AUC0-infinity were linearly related to dose, and t 1/2 was 3 to 4 hours for both groups. There were no obvious differences in the (10-mg) plasma concentration profiles between control subjects and SCI patients. The drug was well tolerated, with only mild and transient side effects of light-headedness, dysesthesias, and dizziness.
Hayes
K C
KC
Department of Physical Medicine and Rehabilitation, University of Western Ontario, Program of Rehabilitation and Geriatric Care, Lawson Health Research Institute, St. Joseph's Health Care London, London, Ontario, Canada.
Katz
M A
MA
Devane
J G
JG
Hsieh
J T C
JT
Wolfe
D L
DL
Potter
P J
PJ
Blight
A R
AR
D015761:4-Aminopyridine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013119:Spinal Cord Injuries / Q000378:metabolism*; D013997:Time Factors
D026902:Potassium Channel Blockers; D015761:4-Aminopyridine