The interaction of flurazepam with diphenylhydantoin in the rat
Sikic, B.I.; Baumel, I.P.
Drug Metabolism and Disposition the Biological Fate of Chemicals 4(6): 584-586
1976
ISSN/ISBN: 0090-9556 PMID: 11981 Document Number: 105873
The effects of various schedules and doses of flurazepam [FZ] on diphenylhydantoin [DPH] plasma half-life and the steady-state plasma and brain levels of DPH were examined in rats. Possible enzyme inducing effects of FZ were also studied. It is likely that the changes in plasma and brain DPH levels observed were due to changes in rate of formation of HPPH, the known major metabolite of DPH in rat and man. The inhibitory effects of FZ on DPH clearance from plasma and brain occurred at the higher FZ dose (40 mg/kg) and not at the lower dose (10 mg/kg). Timing of dosage may also be important in determining whether inhibition or induction by a benzodiazepine is the predominant effect, since DPH half-life after FZ pretreatment decreased when sufficient time had elapsed to allow for clearance of FZ. [The intact animal is a more reliable model for the study of DPH interactions with other drugs than metabolism by 9000 g supernatant fraction or isolated microsomes].