Kinetics of drug action in disease states. IV. Effect of pregnancy on phenobarbital concentrations at onset of loss of righting reflex in rats.

This investigation was designed to determine if the acute hypnotic activity of a barbiturate is altered by advanced pregnancy. Twenty-day-pregnant rats and nonpregnant rats of the same age received an i.v. infusion of phenobarbital, 0.824 mg/min/rat, until they lost their righting reflex. The concentrations of total and free phenobarbital in serum at that time were significantly lower in pregnant than in nonpregnant animals. However, pregnancy had no effect on the concentrations of phenobarbital in the brain and cerebrospinal fluid at onset of loss of righting reflex. The difference of the serum phenobarbital concentrations was due to the slower rate of phenobarbital infusion received by the pregnant rats when normalized for body weight. The lack of difference of phenobarbital concentrations in cerebrospinal fluid, a site that reflects the concentration of the free drug at the sites of action, indicates that advanced pregnancy has no apparent effect on the central nervous system response to phenobarbital.