Delivery of Neostigmine and Glycopyrrolate by Iontophoresis: A Nonrandomized Study in Individuals with Spinal Cord Injury

STUDY DESIGN: Phase I Clinical Trial OBJECTIVES: In this proof-of-principle study, the effectiveness and safety of transdermal administration of neostigmine/glycopyrrolate to elicit a bowel movement was compared to intravenous administration in patients with spinal cord injury. SETTING: James J. Peters Veterans Affairs Medical Center (Bronx, NY) METHODS: Individuals were screened for responsiveness (Physical Response) to intravenous neostigmine (0.03mg/kg)/glycopyrrolate (0.006mg/kg). Intravenous neostigmine/glycopyrrolate responders (Therapeutic Response) were administered low-dose transdermal neostigmine/glycopyrrolate [(0.05mg/kg)/(0.01mg/kg)] by iontophoresis. Non-responders to low-dose transdermal neostigmine/glycopyrrolate were administered high-dose transdermal neostigmine/glycopyrrolate [(0.07mg/kg)/(0.014mg/kg)] by iontophoresis. Bowel movement, bowel evacuation time, and cholinergic side effects were recorded. Visits were separated by 2 to 14 days. RESULTS: Eighteen of 25 individuals (72.0%) had a bowel movement (20±22min) after intravenous neostigmine/glycopyrrolate. Of these 18 individuals, 5 individuals experienced a bowel movement with low-dose transdermal neostigmine/glycopyrrolate. Another 5 individuals had a bowel movement after high-dose transdermal neostigmine/glycopyrrolate administration. Fewer side effects were observed in individuals who received neostigmine/glycopyrrolate transdermally compared to those who were administered intravenous neostigmine/glycopyrrolate. CONCLUSIONS: Transdermal administration of neostigmine/glycopyrrolate by iontophoresis appears to be a practical, safe, and effective approach to induce bowel evacuation in individuals with spinal cord injury.