Correlation of plasma concentration and effects of succinylcholine in dogs

The study was undertaken to determine the pharmacokinetic values for half-life, volume of distribution, and clearance for succinylcholine (SCh) based on measurements of the drug in plasma. Three intravenous (i.v.) doses (0.5, 1.0, and 5.0 mg/kg) were compared to study the time course of paralysis and recovery and to describe the relationship of plasma concentration (Cp) and the pharmacologic effects of SCh in canines. The physiologic response to the neuromuscular blocking drug was monitored using train-of-four stimulation of the left sciatic nerve and recording the response of the corresponding gastrocnemius muscle. Time courses for paralysis and recovery were monitored, and the results were used to predict the kinetic values for the pharmacologic effects. Blood samples were taken following drug administration for direct pharmacokinetic estimations. SCh determinations were performed using ion-pair extraction, chemical demethylation, and gas chromatography with nitrogen phosphorous detection. Both kinetic analyses showed the beta half-life for SCh to be approximately 5 min for all doses. SCh has a distribution half-life of less than 1 min. There appears to be a threshold Cp below which neuromuscular function returns. Recovery following SCh induced paralysis had a rapid onset, but the duration of paralysis and the rate of recovery were especially prolonged for the 5.0-mg/kg treatment group.