Effects of long-term 4-aminopyridine therapy on glucose tolerance and glucokinetics in patients with spinal cord injury.
OBJECTIVE
To assess the effects of the potassium channel blocker, 4-aminopyridine, on glucose tolerance and glucokinetics in patients with spinal cord injury.


METHODS
Prospective, dose level-blinded study.


METHODS
University-affiliated, tertiary-level care, Veterans Affairs medical center, and a university-affiliated research center.


METHODS
Thirty-one patients with spinal cord injury of more than 1 year's duration.


METHODS
In a fasting state, patients ingested 75 g of glucose and completed a 5-hour oral glucose tolerance test before and after 6 months of treatment with an oral, immediate-release formulation of 4-aminopyridine.


RESULTS
The time course of glucose plasma concentrations during the oral glucose tolerance tests was profiled for each patient, and glucokinetic parameters were estimated. Results were compared at baseline and after 6 months of treatment with 4-aminopyridine. Of the 31 patients, 29 (94%) had impaired glucose tolerance at baseline. After 6 months of treatment with 4-aminopyridine, 12 (41%) of the 29 patients had a 2-hour postprandial glucose level that no longer supported a diagnosis of impaired glucose tolerance. No significant changes or clinically important trends were seen in fasting blood glucose concentrations or in other glucokinetic parameters in these patients.


CONCLUSIONS
The long-term administration of an oral, immediate-release formulation of 4-aminopyridine to patients with longstanding spinal cord injury was associated with readily discernible, potentially clinically significant improvements in glucose tolerance. Because impaired glucose tolerance is a common finding in patients with spinal cord injury, more research, including randomized controlled trials with large study populations, is warranted on this potential treatment.
Segal
Jack L
JL
Department of Internal Medicine, Harbor-University of California at Los Angeles Medical Center, Torrance, California 90502, USA. Segaljl@earthlink.net
Thompson
John F
JF
Tayek
John A
JA
D015761:4-Aminopyridine / Q000009:adverse effects / Q000494:pharmacology*; D000328:Adult; D005947:Glucose / Q000493:pharmacokinetics*; D018149:Glucose Intolerance / Q000188:drug therapy; D005951:Glucose Tolerance Test; D006787:Hospitals, Veterans; D006801:Humans; D008875:Middle Aged; D026902:Potassium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology*; D011446:Prospective Studies; D011782:Quadriplegia; D013119:Spinal Cord Injuries / Q000188:drug therapy*
D026902:Potassium Channel Blockers; D015761:4-Aminopyridine; D005947:Glucose