Gender Differences in the Pharmacodynamics of Barbiturates in Rats

There is considerable evidence of gender differences in the pharmacokinetics of numerous drugs, particularly in rodents, but very limited information concerning the effect of gender on pharmacodynamic characteristics (concentration-activity relationships). In this study, heptabarbital or phenobarbital was administered to male and female rats and the concentrations of these drugs in the brain, cerebrospinal fluid and serum at onset or offset of loss of righting reflex were determined. For heptabarbital, offset concentrations were determined in Lewis rats and onset concentrations in Wistar rats. Onset concentrations of phenobarbital were determined in Wistar rats. In all cases, the barbiturate concentrations in males were significantly lower than those in females at the pharmacologic endpoint. The biologic (serum) half-life of heptabarbital is much shorter in males (∼10 min) than in females (∼90 min) and this pharmacokinetic difference is reflected by the considerably longer duration of effect of the drug in females.