title: Phase I safety assessment of intrathecal injection of an American formulation of adenosine in humans.
abstract: BACKGROUND
  Preclinical studies of intrathecal adenosine suggest it may be effective in the treatment of acute and chronic pain in humans. A phase I safety trial of the intrathecal injection of a mannitol-containing formulation of adenosine in Sweden showed a considerable incidence of backache. We performed a phase I safety trial of intrathecal injection of the American formulation of adenosine, which lacks mannitol.
  
  
  METHODS
  Following US Food and Drug Administration and institutional review board approval and written informed consent, 65 volunteers were studied in two trials: an open-label, dose-escalating trial with intrathecal adenosine doses of 0.25-2.0 mg (25 subjects) and a double-blind, placebo-controlled trial of adenosine, 2 mg (40 subjects). Blood pressure, heart rate, end-tidal carbon dioxide, and sensory, motor, and reflex neurologic functions were systematically examined for 24 h after injection, and volunteers were contacted by telephone at times up to 6 months after injection.
  
  
  RESULTS
  Intrathecal adenosine did not affect blood pressure, heart rate, end-tidal carbon dioxide, or neurologic function. Headache was reported by 10 and back pain was reported by 8 of 30 subjects exposed to adenosine in the second double-blind trial, whereas none of these symptoms was reported by the 10 saline-treated subjects.
  
  
  CONCLUSIONS
  These data support further investigation of intrathecal adenosine for analgesia in humans and suggest that this agent does not produce a high incidence of severe side effects.
authors.affiliation: Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. eisenach@wfubmc.edu
authors.forename: James C
authors.initials: JC
authors.lastname: Eisenach
authors.forename: David D
authors.initials: DD
authors.lastname: Hood
authors.forename: Regina
authors.initials: R
authors.lastname: Curry
mesh_terms: D000241:Adenosine / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000700:Analgesics / Q000008:administration & dosage*; D001416:Back Pain / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D007866:Leg; D008297:Male; D010146:Pain / Q000188:drug therapy*
chemical_list: D000700:Analgesics; D000241:Adenosine