Influence of combined treatment with pregnenolone-16α-carbonitrile and spironolactone or phenobarbital on drug metabolism in rats

In female rats, pretreatment with pregnenolone-16α-carbonitrile (PCN), spironolactone or phenobarbital resulted in shorter zoxazolamine and hexobarbital sleeping times and more rapid plasma clearance of zoxazolamine and bishydroxycoumarin. All of these effects were slightly enhanced by simultaneous pretreatment with PCN and spironolactone and greatly increased by concomitant administration of PCN and phenobarbital. However, the observed increases in zoxazolamine and hexobarbital metabolism rates by submitochondrial liver fractions were not further augmented by pretreatment with both of the steroids, while the rates in animals treated with PCN and phenobarbital were only slightly greater than in those which received one of these inducers. It is suggested that PCN and spironolactone share a common receptor and induction mechanism, while the action of phenobarbital is slightly different.