Pharmacokinetics and Pharmacodynamics of Sustained Low-Dose Intravenous Infusions of Pyridostigmine
Abstract
Pyridostigmine bromide may be a useful adjunct to atropine sulfate to prevent death from organophosphate exposure if given in advance of the exposure and if given in a dose that is adequate to inhibit red blood cell acetylcholinesterase by 20-40%. The inter-individual variability to a known, constant exposure to pyridostigmine is poorly characterized. This study was designed (1) to assess the relationship between plasma concentrations of pyridostigmine and erythrocyte acetylcholinesterase inhibition, (2) to determine whether erythrocyte acetylcholinesterase and the contractile response of the iris to light are inhibited in a parallel fashion by pyridostigmine, and (3) to assess the inter-individual variations in the concentration-effect relationships described in 1 and 2. The clinical portion of the study was conducted between 27 July and 16 October 1987, and showed that the constant intravenous infusion of low doses of pyridostigmine was safe and well tolerated. Intravenous pyridostigmine gave steady plasma concentrations of pyridostigmine and erythrocyte acetylcholinesterase inhibition. Mean peak erythrocyte acetylcholinesterase inhibitions were 29% and 36% for infusions of 12.5 mcg/minute and 18.75 mcg/minute, respectively. The mean rate constant of elimination from the central compartment was 1.365 hr(exp -1), corresponding to an elimination half-life of 30 minutes. The mean plasma clearance was 44.62 L/hr, or 744 ml/minute. The mean concentration at which 50% of the erythrocyte acetylcholinesterase activity was inhibited (IC sub 50) was 31.8 ng/ml. The influence of these infusions on the contractile response of the iris was difficult to measure and was not consistent within subjects and no correlation with plasma pyridostigmine levels or acetylcholinesterase inhibition could be established.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 17, 1993
- Accession Number
- ADA530411
Entities
People
- Brent G. Petty
- David M. Kornhauser
- Paul S. Lietman
Organizations
- Johns Hopkins University