title: Absorption characteristics of sustained-release 4-aminopyridine (fampridine SR) in patients with chronic spinal cord injury.
abstract: Fampridine SR (4-aminopyridine) is a potassium channel-blocking drug currently being investigated for its therapeutic efficacy in ameliorating central conduction deficits due to demyelination in patients with spinal cord injury (SCI). The present open-label pharmacokinetic trial examined the absorption characteristics of a sustained-release form of the drug in 25 SCI subjects with chronic incomplete injuries. The overall group mean Cmax of 27.7 +/- 6.2 ng/mL occurred at a tmax of 3.4 +/- 1.4 hours. AUC0-12 was 210.5 +/- 49.5 ng/mL.h. For paraplegics, AUCtmax was 76.02 +/- 33.28 and for tetraplegics was significantly less at 51.25 +/- 20.36 (p = 0.037). A statistically significant difference in the initial rate and extent of absorption, but not in total 4-AP bioavailability over the 12-hour study period, was evident between tetraplegic patients, 0.60 +/- 0.23, and paraplegic patients, 0.39 +/- 0.14 (p = 0.02). There was a linear correlation (p < 0.05) between the neurological level of injury and Cmax/AUCtmax. These results confirm and extend previous observations of different rates of drug absorption among SCI patients with lesions above and below the sympathetic outflow (T6) and provide evidence of the absorption characteristics of this sustained-release form of 4-aminopyridine, which is helpful for optimal dosing.
authors.affiliation: Department of Veterans Affairs Medical Center, Long Beach, California 90822, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Segal
authors.forename: K C
authors.initials: KC
authors.lastname: Hayes
authors.forename: S R
authors.initials: SR
authors.lastname: Brunnemann
authors.forename: J T
authors.initials: JT
authors.lastname: Hsieh
authors.forename: P J
authors.initials: PJ
authors.lastname: Potter
authors.forename: M S
authors.initials: MS
authors.lastname: Pathak
authors.forename: D S
authors.initials: DS
authors.lastname: Tierney
authors.forename: D
authors.initials: D
authors.lastname: Mason
mesh_terms: D015761:4-Aminopyridine / Q000097:blood / Q000493:pharmacokinetics*; D000042:Absorption; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002908:Chronic Disease; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010264:Paraplegia / Q000097:blood / Q000473:pathology; D011782:Quadriplegia / Q000097:blood / Q000473:pathology; D012720:Severity of Illness Index; D013119:Spinal Cord Injuries / Q000097:blood* / Q000473:pathology; D013997:Time Factors
chemical_list: D003692:Delayed-Action Preparations; D015761:4-Aminopyridine