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Safety and Efficacy of 4‐Aminopyridine in Humans with Spinal Cord Injury: A Long‐Term, Controlled Trial
Author(s) -
Segal Jack L.,
Pathak Mayank S.,
Hernandez Jesus P.,
Himber Peter L.,
Brunnemann Sherry R.,
Charter Richard S.
Publication year - 1999
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.19.9.713.31540
Subject(s) - medicine , spasticity , anesthesia , spinal cord injury , randomized controlled trial , dose , 4 aminopyridine , spinal cord , veterans affairs , physical therapy , surgery , psychiatry , potassium channel
Study Objective. To determine the effects of the long‐term administration of 4‐aminopyridine (4‐AP) on sensorimotor function in humans with longstanding spinal cord injury (SCI). Design. Randomized, open‐label, active‐treatment control, dosage‐blinded study. Setting. University‐affiliated, tertiary‐level care, Department of Veterans Affairs Medical Center. Patients. Twenty‐one healthy men and women outpatients suffering from traumatic SCI (14 tetraplegic, 7 paraplegic) for 2 years or more. Interventions. Dosages of an immediate‐release formulation of 4‐AP were titrated. At 3 months, 16 subjects were receiving 4‐AP 30 mg/day (high dose); 5 subjects were receiving 4‐AP 6 mg/day (low dose) and served as an active‐treatment control group. Measurements and Main Results. Composite motor and sensory scores had statistically significant increases at 3 months. Maximal expiratory pressure, maximal inspiratory pressure, forced vital capacity, and forced expiratory volume in 1 second showed clinically meaningful and/or statistically significant increases among patients receiving 4‐AP 30 mg/day. These subjects also had significant decreases in spasticity (modified Ashworth Scale). Serial biochemical profiles and electroencephalographs were unchanged from baseline, and no clinically significant drug toxicity was encountered. Conclusions. Long‐term oral administration of immediate‐release 4‐AP was associated with improvement in and recovery of sensory and motor function, enhanced pulmonary function, and diminished spasticity in patients with long‐standing SCI. 4‐Aminopyridine appears to be safe and relatively free from toxicity when administered orally over 3 months. Each patient who received immediate‐release 4‐AP 30 mg/day showed a response in one or more of the outcome measures.