Intravenous infusion of 4-AP in chronic spinal cord injured subjects

Abstract

Study design: A prospective double blind cross over trial of intravenous 4-Aminopyridine (4-AP). Objective: To determine the ecacy of this drug in the treatment of spinal cord injured (SCI) patients for neurologic impairment, pain and spasticity. Setting: The post anesthesia care unit (PACU) of a tertiary care acute hospital. Methods: Twelve paraplegic patients were enrolled in a double blind cross over intravenous trial of 4-Aminopyridine (4-AP). Thirty milligrams of 4-AP or placebo were administered over a 2 h period. Patients were serially examined during and after the infusion clinically for pain, sensorimotor function, hypertonicity and motor control using electromyography (EMG). Samples of blood and cerebrospinal¯uid (CSF) were also analyzed at similar intervals. Results: Despite penetration of 4-AP into the CSF, no signi®cant dierences were noted in the clinical and EMG parameters at the times measured. Individual changes in sensory function were reported by some patients in both the placebo and 4-AP trials, however mean values were not robust. Frequently, patients complained of unpleasant symptoms during the 4-AP infusion. Conclusion: The intravenous route may not be the best way to administer this drug as no short term bene®ts were observed. Spinal Cord (2000) 38, 7 ± 15

Effect of 4-aminopyridine on gait in ambulatory spinal cord injuries: a double-blind, placebo-controlled, crossover trial

“…However, the medication duration could have been longer, as suggested by positive participant feedback. Past researchers have reported that carryover may last up to 48 h. 3,11,13 Currently, the optimum dosage and administration for 4-AP remains unclear. 33 A complete dose response curve has not yet been investigated.…”

“…The 4-AP (Fampridine-SR) group revealed improved sensation and responded more positively to the drug efficacy and improved quality of life due to the medication. In a similarly designed crossover study, Donovan et al 13 investigated nonambulatory, chronic SCI subjects and found no evidence of superior gains in the group receiving 30 mg intravenous 4-AP on motor, sensory, spasticity and pain scores.…”

Intrathecal administration of 4-aminopyridine in chronic spinal injured patients

“…Peak concentrations of 121 and 162 ng/ml seen in two of the subjects were equivalent to peak plasma levels seen in previous studies of maximal tolerable systemic doses. 5 On the other hand, data from the intravenous portion of this study 13 indicate that the concentration expected in the CSF is only about 50% of that seen in the plasma, therefore the local concentrations achieved seem likely to be higher than those that have been produced with systemic administration. These local concentrations appeared to be su cient to produce localized increases in re¯ex responses to Figure 2 Concentration of 4-aminopyridine in the cerebrospinal¯uid taken from two subjects before, during, and after intrathecal infusion of 4-aminopyridine at a rate of 5 mg/h cutaneous stimulation, and even su cient to focal muscle fasciculation, but did not clearly lead to clinically useful improvements in function.…”

“…13 These patients had been recruited from a population of chronic spinal cord injury patients referred to The Institute for Rehabilitation and Research for their rehabilitation care including the management of problems related to pain and/or spasticity.…”

“…This followed an initial double-blind, crossover study that examined the e ects of intravenous 4-AP compared with vehicle placebo in a group of 12 patients. 13 Both studies were carried out with the approval of the Institutional Review Board of Baylor College of Medicine.…”