KINETICS OF DRUG-ACTION IN DISEASE STATES .4. EFFECT OF PREGNANCY ON PHENOBARBITAL CONCENTRATIONS AT ONSET OF LOSS OF RIGHTING REFLEX IN RATS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 232  (2) , 426-429
Abstract
The acute hypnotic activity of a barbiturate was studied to determine if it is altered by advanced pregnancy. Pregnant rats (20 day) 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. Pregnancy had no effect on the concentrations of phenobarbital in the brain and CSF 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 wt. The lack of difference of phenobarbital concentrations in CSF, 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 CNS response to phenobarbital.