Mechanisms of Action and Pharmacokinetics of Physostigmine in Relation to Acute Intoxication by Organofluorophosphates

摘要

This report deals with several independent studies. The distribution of radioactivity (RA) in different organs after oral administration of physostigmine (Phy) showed that the RA was maximum in liver followed by kidney and lung, whereas the percentage of the administered dose in terms of RA was maximum in muscle, followed by liver, after i.v. administration. Phy and its metabolites appear to penetrate brain cell membranes and concentrate in intracellular organelles. The drug and its metabolites appear to be concentrated in mitochondria in greater amounts by a mechanism other than simple diffusion. A semilog plot of % cholinesterase (ChE) inhibition in diaphram vs. time gave rate of recovery of the enzyme (0.02/min) after i.m. administration. The rate of recovery was biphsic after oral administration, fast phase being 0.053/min and slow phase being 0.017/min. Regions with a high ChE activity showed greater retention of Phy over time gave than those with low activity of the enzyme. This greater retention may be due to the binding to the enzyme. Some brain regions equilibrated rapidly with Phy showed the highest concentration initially and then declined gradually up to 12 min. the elimination rate constants of Phy from these regions ranged from 0.058 to 0.18/min. Keyword: GD agent. (aw)