Safety Tolerance Pharmacokinetics and Pharmacodynamics of Intravenous Pyridostigmine in Healthy Men and the Influence of Food on Oral Pyridostigmine Pharmacokinetics
Abstract
Pyridostigmine bromide may be a useful agent to prevent death from organophosphate exposure if given in advance or the exposure and if given in a dose that is adequate to inhibit red blood cell acetylcholinesterase by 20- 40%. Previous studies conducted at our institution determined that single doses of pyridostigmine bromide administered as syrup inhibited red blood cell acetylcholinesterase by 20-40% longer than equivalent doses of various "sustained-release" tablets and capsules, but syrup is inconvenient in a field situation. The best experimental sustained-released formulation (45 mg capsule) kept red blood cell acetylcholinesterase inhibition above 20% for four hours. In an effort to find a formulation that would provide adequate acetylcholinesterase inhibition for a longer period, other formulations are being investigated. This study was designed (1) to characterize the pyridostigmine bromide pharmacokinetics in healthy men after single doses of two oral dosage forms of pyridostigmine bromide, one a sustained-release preparation and the other a standard tablet, and compare these to the pharmacokinetics of a prolonged intravenous pyridostigmine infusion, (2) to characterize the time course of red blood cell acetylcholinesterase inhibition following the administration of these two oral dosage forms and compare these to the inhibition occurring with intravenous pyridostigmine, (3) to assess the effect of food on the pharmacokinetics and pharmacodynamics of the two oral pyridostigmine dosage forms, and (4) to assess the safety, tolerance, pharmacokinetics, and pharmacodynamics of multiple doses of the oral formulations over two days.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 17, 1991
- Accession Number
- ADA640656
Entities
People
- Brent G. Petty
- David M. Kornhauser
- Paul S. Lietman
Organizations
- Johns Hopkins University