Effect of premedication with acetylpromazine on the disposition kinetics of thiopental

This study was performed to determine whether premedication with acetylpromazine alters the disposition kinetics of thiopental in normal dogs. Based on nonlinear least squares regression analysis of the plasma concentration-time data obtained in individual dogs, a three-compartment open model was selected to describe the pharmacokinetic behavior of thiopental. While clinically premedication appears to delay time of awakening from thiopental anesthesia, statistical comparison (Student's t-test for paired data) of pharmacokinetic terms showed no significant difference. This may be largely attributed to wide individual variation in each parameter. The rate of change in volume of distribution at zero time (mean +/- SD, n = 7), which is a parameter that might have been expected to vary significantly, was 97 +/- 106 ml/min X kg for thiopental alone and 77 +/- 60 ml/min X kg following acetylpromazine premedication. Body clearance of thiopental was 1.96 +/- 0.59 ml/min X kg in dogs without premedication and 1.55 +/- 0.49 ml/min X kg following acetylpromazine. By relating observed time of awakening to plasma concentrations of thiopental it was determined that awakening from anesthesia occurred at a concentration of 20 micrograms/ml whether or not the dogs were premedicated. It can only be concluded that while premedication with acetylpromazine appears to delay time of awakening from anesthesia, it does not change the disposition kinetics of thiopental or affect the plasma concentration at the observed time of awakening.