Absorption characteristics of sustained-release 4-aminopyridine (fampridine SR) in patients with chronic spinal cord injury

Fampridine SR (4-aminopyridine) is a potassium channel-blocking drug curren tly being investigated for its therapeutic efficacy in ameliorating central conduction deficits due to demyelination in patients with spinal cord inju ry (SCI). The present open-label pharmacokinetic trial examined the absorpt ion characteristics of a sustained-release form of the drug in 25 SCI subje cts with chronic incomplete injuries. The overall group mean C-max of 27.7 +/- 6.2 ng/mL occurred at a t(max) of 3.4 +/- 1.4 hours. AUC(0-12) was 210. 5 +/- 49.5 ng/mL.h. For paraplegics, AUCt(max) was 76.02 +/- 33.28 and for tetraplegics was significantly less at 51.25 +/- 20.36 (p = 0.037). A stati stically significant difference in the initial rate and extent of absorptio n, but not in total 4-AP bioavailability over the 12-hour study period, was evident between tetraplegic patients, 0.60 +/- 0.23, and paraplegic patien ts, 0.39 +/- 0.14 (P = 0.02). There was a linear correlation (p < 0.05) bet ween the neurological level of injury and C-max/AUCt(max). These results co nfirm and extend previous observations of different rates of drug absorptio n among SCI patients with lesions above and below the sympathetic outflow ( T-6) and provide evidence of the absorption characteristics of this sustain ed-release form of 4-aminopyridine, which is helpful for optimal dosing. Jo urnal of Clinical Pharmacology 2000;40:402-409 (C)2000 the American College of Clinical Pharmacology.