Dose–Response and Plasma Concentration–Response Relationships of Pancuronium in Man

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Abstract
The dose-response and plasma concentration-response relationships for pancuronium in man were studied during its i.v. administration to 8 patients at a rate of 1.62 .mu.g/kg per min. The (log) dose-response relationships caused a sigmoid curve that was linear in its central range. At 20, 50 and 80% paralysis the cumulative dosages (mean .+-. SEM [standard error of the mean]) were 0.04 (.+-. 0.01), 0.06 (.+-. 0.01), and 0.08 (.+-. 0.02) mg/kg, respectively. Administration of pancuronium, 56 .mu.g/kg, to another 12 patients at a more rapid rate caused a maximum intensity of blockade of more than 50%. The (log) plasma concentration-response curve was not parallel to the dose-response curve, with mean (.+-. SEM) concentrations at 20, 50 and 80% paralysis of 0.21 (.+-. 0.04), 0.25 (.+-. 0.04) and 0.30 (.+-. 0.40) .mu.g/ml, respectively, during the onset of paralysis. After cessation of the infusion, plasma concentrations of pancuronium were usually lower for the same intensity of paralysis. Using data for the entire response range during recovery from paralysis, the mean effective plasma concentration of pancuronium for a 50% response was 0.20 .mu.g/ml. Recovery from blockade to 95% paralysis (5% of control twitch height) was associated with a plasma concentration of 0.25 .mu.g/ml, a value in agreement with plasma concentrations obtained after a single bolus administration of pancuronium, 6 mg, to 30 patients. For 27 patients the rate of decline of paralysis from 80 to 20% showed a highly statistically significant relationship to the apparent rate of decline in the plasma concentrations of pancuronium.