Absorption Characteristics of Sustained-Release 4-Aminopyridine (Fampridine SR) in Patients with Chronic Spinal Cord Injury

Fampridine SR (4-aminopyridine) is a potassium channelblocking drug currently being investigated for its therapeutic efficacyin 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-releaseform of the drug in 25 SCI subjects with chronic in complete injuries. The overall group mean C sub(max) of 27.7 c 6.2 ng/mL occurred at a t sub(max) of 3.4 c 1.4 hours. AUC sub(0.12)was 210.5 c 49.5 nglmL; h. Forparaplegics, AUCt sub(max) was 76.02 c 33.28 and for tetraplegics was significantly less at 51.25 c 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 c 0.23, and paraplegic patients, 0.39c 0.14 (p = 0.02). There was a linear correlation (p < 0.05) between the neurological level of injury and C sub(max)/AUCt sub(max). These results confirm and extend previous observations of different rates of drug absorption among SCI patients with lesions above and below the sympathetic outflow(T sub(6)) and provide evidence of the absorption characteristics of this sustained-release form of 4-aminopyridine, which is helpfulfor optimal dosing.