6-beta-hydroxycortisol and Dizziness

6-beta-hydroxycortisol has been researched along with Dizziness* in 1 studies

Trials

1 trial(s) available for 6-beta-hydroxycortisol and Dizziness

ArticleYear
Induction of tirilazad clearance by phenytoin.
    Biopharmaceutics & drug disposition, 1998, Volume: 19, Issue:2

    Tirilazad is a membrane lipid peroxidation inhibitor being studied for the management of subarachnoid hemorrhage; phenytoin is used for seizure prophylaxis in the same disorder. The induction of tirilazad clearance by phenytoin was assessed in 12 volunteers (6 male, 6 female). Subjects received phenytoin orally every 8 h for 7 days (200 mg for nine doses and 100 mg for 13 doses) in one phase of a crossover study. In both study phases, 1.5 mg kg-1 tirilazad mesylate was administered by i.v. infusion every 6 h for 29 doses. Tirilazad mesylate and U-89678 (an active metabolite) in plasma were quantified by HPLC. After the final dose, tirilazad clearance was increased by 91.8% in subjects receiving phenytoin + tirilazad versus tirilazad alone. AUC0-6 for U-89678 after the last tirilazad dose was reduced by 93.1% by concomitant phenytoin. These effects were statistically significant. The time course of induction was consistent with that of phenytoin's effect on the ratio of urinary 6 beta-hydroxycortisol to cortisol, a measure of hepatic CYP3A activity. The results show that phenytoin induces metabolism of tirilazad and U-89678 in healthy subjects and that, under these conditions, tirilazad clearance approaches liver blood flow.

    Topics: Adult; Anticonvulsants; Antioxidants; Ataxia; Cross-Over Studies; Dizziness; Dose-Response Relationship, Drug; Drug Interactions; Female; gamma-Glutamyltransferase; Humans; Hydrocortisone; Injections, Intravenous; Male; Middle Aged; Motor Activity; Nystagmus, Pathologic; Phenytoin; Phosphoric Monoester Hydrolases; Pregnatrienes; Sleep Stages; Time Factors

1998