PHARMACOKINETIC ANALYSIS OF THE EFFECT OF VECURONIUM IN SURGICAL PATIENTS - PHARMACOKINETIC AND PHARMACODYNAMIC MODELING WITHOUT PLASMA-CONCENTRATIONS

Background: Methods of the kinetic analysis of vecuronium based on eff ect only were developed but have been limited by the short time period of the studies. Using a multicompartment model and sequential dosing, the authors studied the ability of tests to determine most pharmacoki netic and pharmacodynamic parameters of vecuronium without measuring p lasma concentrations. Methods: The time course of neuromuscular blocka de by successive bolus doses of vecuronium was recorded using electrom yography. Inhibition of neuromuscular transmission by vecuronium was m odeled by a biexponential decline in the concentrations in the central compartment and first-order transfer between the central and the effe ct compartments responsible for the inhibition of the first (T1) and f ourth (T4) responses to train-of-four stimulation. Results: The time c ourse of the effect of vecuronium was described well by the model. The mean half-lives of equilibration between plasma and the effect compar tments to inhibit T1 and T4 were 2.5 and 3.2 min, respectively. The me an half-lives of distribution and elimination from the central compart ment were 7.7 and 78 min, respectively. From the kinetic and dynamic p arameters calculated after two and three doses, the time taken to reco ver to 50% of the maximal block of T1 was predicted for the succeeding dose. The mean prediction errors (100 x [absolute difference between actual and predicted times]/actual) were 13.6% (range, 0-40%) and 15% (range, 0-25%) after three and four doses, respectively. Conclusions: After sequential doses, measurement of the time course of the effect o f vecuronium yields pharmacokinetic and pharmacodynamic parameters wit h clinically acceptable accuracy in individual patients.