Urinary excretion of 6 beta-hydroxycortisol as an in vivo marker for CYP3A induction: applications and recommendations.
In: Clinical pharmacology and therapeutics, Jg. 63 (1998-06-01), Heft 6, S. 617-22
Online
academicJournal
Zugriff:
Objective: To evaluate the usefulness of 6 beta-hydroxycortisol as a screen for CYP3A induction in early-phase drug development.
Methods: Five groups of 12 healthy elderly men were randomized to one of five treatment regimens: (1) 600 mg rifampin (INN, rifampicin) once daily, (2) placebo once daily, (3) 40 mg SB 216469 twice a day, (4) 60 mg SB 216469 twice a day, or (5) 40 mg SB 216469 three times a day. All medications were taken orally and administered for 7 consecutive days. Urine was collected over a 24-hour period for each subject before administration and on the last day of administration for each respective regimen for measurement of 6 beta-hydroxycortisol and 17-hydroxycorticosteroid concentrations.
Results: Subjects in the rifampin group had a significant increase from predose value in the 24-hour urinary excretion of 6 beta-hydroxycortisol and the ratio of 6 beta-hydroxycortisol to 17-hydroxycorticosteroid. All 12 subjects in the rifampin group had increases in 6 beta-hydroxycortisol excretion, whereas 11 of 12 had an increase in the ratio. The placebo and three active treatment groups did not show significant changes in either parameter.
Conclusions: Urinary excretion of 6 beta-hydroxycortisol may be useful as a screening tool in early-phase development to assess the potential for an investigational drug to induce CYP3A.
Titel: |
Urinary excretion of 6 beta-hydroxycortisol as an in vivo marker for CYP3A induction: applications and recommendations.
|
---|---|
Autor/in / Beteiligte Person: | Kovacs, SJ ; Martin, DE ; Everitt, DE ; Patterson, SD ; Jorkasky, DK |
Link: | |
Zeitschrift: | Clinical pharmacology and therapeutics, Jg. 63 (1998-06-01), Heft 6, S. 617-22 |
Veröffentlichung: | 2015- : Hoboken, NJ : Wiley ; <i>Original Publication</i>: St. Louis : C.V. Mosby, 1998 |
Medientyp: | academicJournal |
ISSN: | 0009-9236 (print) |
DOI: | 10.1016/S0009-9236(98)90084-4 |
Schlagwort: |
|
Sonstiges: |
|