Pharmacokinetic studies of single and multiple oral doses of fampridine-SR (sustained-release 4-aminopyridine) in patients with chronic spinal cord injury.

Fampridine (4-aminopyridine) is a potassium channel blocking agent that restores conduction in demyelinated axons and improves neurologic function in patients with chronic spinal cord injury (SCI). Based on the pharmacokinetic profile of orally administered fampridine, multiple daily doses (4 or more) would need to be taken to sustain its therapeutic effects. Two studies were conducted to determine the pharmacokinetics and safety profile of an oral, sustained-release (SR) formulation of fampridine (fampridine-SR, 10-25 mg) administered as a single dose (n = 14) and twice daily for 1 week (n = 16) in patients with chronic, incomplete SCI. Mean plasma concentrations and area under the plasma concentration-time curve were proportional to the dose administered, whereas other pharmacokinetic parameters were independent of dose. Fampridine-SR was absorbed slowly (peak plasma concentration shortly after dosing, 2.6-3.7 hours) and eliminated (plasma half-life, 5.6-7.6 hours), and reached steady state after 4 days of twice-daily administration. Fampridine-SR was well tolerated, with only mild to moderate adverse events reported, and no serious adverse events. The extended plasma half-life of fampridine-SR allows convenient twice-daily dosing. Clinical trials designed to assess neurologic and functional improvement using fampridine-SR in patients with chronic SCI are currently underway.

Visceral adipose tissue and the ratio of visceral to subcutaneous adipose tissue are greater in adults with than in those without spinal cord injury, despite matching waist circumferences.

BACKGROUND: Abdominal obesity, particularly visceral adipose tissue (VAT), is associated with an increased risk of coronary heart disease (CHD). Despite an elevated risk of CHD mortality in persons with spinal cord injury (SCI), neither abdominal adipose tissue accumulation nor the validity of waist circumference (WC) has been determined in persons with SCI. OBJECTIVES: The objectives of this study were to compare total adipose tissue (TAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and the ratio of VAT to SAT (VAT:SAT) between adults with SCI and age-, sex-, and WC-matched able-bodied (AB) controls and to determine the relation between WC and VAT in both groups. DESIGN: Thirty-one men and women (n = 15 SCI and 16 AB) with a mean (+/-SD) age of 38.9 +/- 7.9 y participated in this cross-sectional study. Abdominal adipose tissue was quantified by computed tomography at L4-L5. WC was measured at 3 sites: lowest rib, iliac crest, and the midpoint between the lowest rib and iliac crest. RESULTS: Persons with SCI had a 58% greater mean VAT (P = 0.003), 48% greater mean VAT:SAT (P = 0.034), and 26% greater mean TAT (P = 0.055) than did matched AB controls after differences in weight were accounted for. Mean SAT was not significantly different between groups. WC at all sites was correlated with VAT in both groups (SCI: 0.905 < or = r < or = 0.925; AB: 0.838 < or = r < or = 0.877; both P < 0.001). CONCLUSIONS: High levels of VAT exist in young people with SCI who classify themselves as active and healthy. WC may be a valid surrogate measure of VAT in this population and serve as a tool for clinicians to identify those at risk of CHD.

Can body weight supported treadmill training increase bone mass and reverse muscle atrophy in individuals with chronic incomplete spinal cord injury?

This study evaluates the impact of 12 months of body weight supported treadmill training (BWSTT) on muscle and bone in individuals with spinal cord injury (SCI). Fourteen individuals who sustained an incomplete SCI at least 12 months before the study were recruited to participate in BWSTT 3 times/week for a total of 144 sessions. Thirteen individuals completed the study. The average age of subjects was 29 y, average time post-injury was 7.70 y (range: 1-24 y). Areal bone densities of the proximal and distal femur, proximal tibia, spine, and whole body were measured using dual-energy X-ray absorptiometry. Muscle cross-sectional area (CSA), volumetric bone density, and bone geometry at mid-femur and proximal tibia were measured using computed tomography. Serum osteocalcin and urinary deoxypyridinoline were measured at baseline and after 6 and 12 months of training. All other measures were made before and after training. Participants experienced significant increases in whole-body lean mass, from 45.9 +/- 8.7 kg to 47.8 +/- 8.9 kg (mean +/- SD; p < 0.003). Muscle CSAs increased by an average of 4.9% and 8.2% at the thigh and lower leg sites, respectively. No significant changes occurred in bone density or bone geometry at any site, or in bone biochemical markers. Whole-body bone density exhibited a small but statistically significant decrease (p < 0.006). BWSTT may therefore be a promising intervention for increasing muscle mass. Although 12 months of BWSTT did not increase bone density in individuals with chronic incomplete SCI, it did not appear to decrease bone density at fracture-prone sites.