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Effects of Long‐term 4‐Aminopyridine Therapy on Glucose Tolerance and Glucokinetics in Patients with Spinal Cord Injury
Author(s) -
Segal Jack L.,
Thompson John F.,
Tayek John A.
Publication year - 2007
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.27.6.789
Subject(s) - medicine , spinal cord injury , impaired glucose tolerance , anesthesia , spinal cord , randomized controlled trial , 4 aminopyridine , postprandial , glucose tolerance test , surgery , insulin , insulin resistance , potassium channel , psychiatry
Study Objective . To assess the effects of the potassium channel blocker, 4‐aminopyridine, on glucose tolerance and glucokinetics in patients with spinal cord injury. Design . Prospective, dose level–blinded study. Setting . University‐affiliated, tertiary‐level care, Veterans Affairs medical center, and a university‐affiliated research center. Patients . Thirty‐one patients with spinal cord injury of more than 1 year's duration. Intervention . 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. Measurements and Main 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.