Effects of phenobarbital on thiopental pharmacokinetics in greyhounds

The effects of phenobarbital on the pharmacokinetics of thiopental (15 mg/kg IV) were investigated in 12 trained racing Greyhounds. Phenobarbital (16 mg/kg of body weight, PO, q 24 h), administered for 14 days, reduced the area under the curve of plasma concentration of thiopental vs time from 10,688 micrograms.min/ml to 3,224 micrograms.min/ml. Furthermore, the time to recovery from anesthesia (ie, return to standing position) decreased from 103 minutes to 35.7 minutes after phenobarbital. These effects were attributed to an increase in the metabolic clearance of thiopental, as a result of induction of liver enzyme activity by phenobarbital. These results suggested that hepatic metabolism, in addition to distribution, is a factor that must be considered when assessing the difference in drug disappearance rates between Greyhounds and other breeds of dogs.