PT  - JOURNAL ARTICLE
AU  - J. Andrew Williams
AU  - Richard J. Chenery
AU  - Theo A. Berkhout
AU  - Gabrielle M. Hawksworth
TI  - Induction of Cytochrome P4503A by the Antiglucocorticoid Mifepristone and a Novel Hypocholesterolaemic Drug
DP  - 1997 Jun 01
TA  - Drug Metabolism and Disposition
PG  - 757--761
VI  - 25
IP  - 6
4099  - http://dmd.aspetjournals.org/content/25/6/757.short
4100  - http://dmd.aspetjournals.org/content/25/6/757.full
SO  - Drug Metab Dispos1997 Jun 01; 25
AB  - Rat liver microsomal testosterone (250 μM) hydroxylation and immunoreactive CYP3A protein were compared after administration of the antiglucocorticoid RU 486 (50 mg·kg−1·day−1for 4 days) and the hypocholesterolaemic drug SR-12813 (150 mg·kg−1·day−1for 4 days). Markers of CYP3A-mediated enzyme activity (testosterone 15β-, 6β-, and 2β-hydroxylation) were increased after administration of both drugs. Testosterone 6β-hydroxylation was increased 5-fold by RU 486 and 9-fold by SR-12813. Administration of dexamethasone alone at 150 mg·kg−1·day−1or in combination with RU 486 induced testosterone 6β-hydroxylation 15- to 20-fold. The lack of antagonistic effect of RU 486 on dexamethasone-mediated CYP3A induction strengthens support for the hypothesis that the “classical glucocorticoid receptor” does not play a part in this process. The induction of CYP3A enzymes by the bisphosphonate SR-12813 suggests the existence of a new class of compounds with CYP3A inducing properties. The American Society for Pharmacology and Experimental Therapeutics