Relationship between decay of plasma concentration of fazadinium and recovery from its neuromuscular blocking effect

The relationship of the time-course of the decay of plasma concentration of fazadinium and neuromuscular block has been investigated after i.v. administration of 0.75 mg kg-1 to six anaesthetized patients. The pharmacokinetics of fazadinium were analysed according to a two-compartment open model. A significant correlation was found between the plasma concentration of fazadinium and the twitch height (TH) values during recovery from the block (P less than 0.001). The mean total plasma concentrations for 25, 50 and 75% TH recovery were: 1.90 +/- 0.17; 1.44 +/- 0.18 and 1.08 +/- 0.12 microgram ml-1, respectively. Elapsed time between fazadinium administration and the TH recovery to 50% (0-TH50) and the recovery period TH25-75 were 47 +/- 4 min and 25 +/- 2 min, respectively. Plasma log decay rate of fazadinium during TH25-75 period (Kapp 25-75) was: 0.0249 +/- 0.0032 min-1. Significant correlations (P less than 0.01) were observed between the elimination rate constant (k10) of the pharmacokinetic model, Kapp 25-75 (P less than 0.01) and the pharmacodynamic parameters: time interval 0-TH50 and recovery rate TH25-75. These results showed that part of the individual pharmacodynamic variation had its origin in the interindividual pharmacokinetic variation.