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- Title
PII-51.
- Authors
Lee, R. D.; Witt, G.; Chwalisz, K.
- Abstract
Background: Asoprisnil (J867) is a novel selective progesterone receptor modulator (SPRM) with partial or mixed agonist/antagonist effects depending on the biological action studied. Previous studies using human liver microsomes have shown that the metabolism of asoprisnil to its J912 metabolite involves CYP2C8 and CYP3A. The objective of this study was to evaluate the effect of a potent inhibitor and inducer of CYP3A/CYP on the pharmacokinetics (PK) of asoprisnil.Method: In these open-label sequential drug-drug interaction studies, two groups of 24 female subjects received a single 25 mg oral dose of asoprisnil before and after multiple oral doses of 400 mg ketoconazole or 600 mg rifampin for 5 or 6 days, respectively. Serial blood samples on asoprisnil dosing days were obtained over 30 hours to determine the PK of asoprisnil and J912. Plasma concentrations of asoprisnil and J912 were determined using a validated LC/MS/MS assay.Results: The 90% confidence intervals (CI) for the ratios of the central values of asoprisnil or J912 Cmax and AUC were not contained within the no effect boundaries of 0.80-1.25 when asoprisnil was coadministered with either ketoconazole or rifampin. All treatments were safe and generally well tolerated. (See Table)Conclusion: Concomitant administration of 25 mg asoprisnil after multiple daily doses of ketoconazole or rifampin significantly affect the PK of asoprisnil and its J912 metabolite, and therefore, coadministration is not recommended without appropriate dose adjustments.Clinical Pharmacology & Therapeutics (2005) 79, P49–P49; doi: 10.1016/j.clpt.2005.12.176
- Subjects
KETOCONAZOLE; RIFAMPIN; PHARMACOKINETICS; EXPERIMENTAL pharmacology; CLINICAL trial registries; CLINICAL drug trials
- Publication
Clinical Pharmacology & Therapeutics, 2006, Vol 79, Issue 2, pP49
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1016/j.clpt.2005.12.176