Relationship between pharmacokinetics and pharmacodynamics of fazadinium in rabbits

The disposition of 1,1'-azobis-3-methyl-2-phenyl-1H-imidazo-[1,2-a] pyridinium dibromide (fazadinium) was studied in 10 rabbits receiving a single i.v. dose of 1 mg/kg of the drug. The serum, bile and urine concentrations were determined by a spectrofluorimetric method. The neuromuscular blocking agent follows a three-compartment open kinetic model with values of the disposition macroconstants of alpha = 12.66 h-1, beta = 2.150 h-1 and gamma = 0.150 h-1. The effect of fazadinium on the average amplitude of diaphragm contraction was studied. From the disappearance rate of the pharmacological effect the slow disposition constant was determined (gamma = 0185 h-1). There are no statistically significant differences for a probability level of p = 0.05 with the values established from the plasma levels.