Assessment of CYP3A and UGT enzyme activity
Activity was assessed in subcellular fractions prepared from female Sprague-Dawley rats after a daily oral administration of L-742694 (50 mg/kg), DEX (50 mg/kg/day), or 0.25% methylcellulose as vehicle control (CON) for 4 days. All values are presented as mean ± S.E.M.
| Treatment Groups | ||||||
|---|---|---|---|---|---|---|
| CON | L-742694 | DEX | ||||
| Activity | Liver | Small Intestine | Liver | Small Intestine | Liver | Small Intestine |
| 6β-Hydroxytestosterone (pmol/min/mg)a | 139.8 ± 18.6 | N.A. | 1185.1 ± 374.5* | N.A. | 6012.8 ± 1876.4* | N.A. |
| Ethinyl estradiol-3-O-glucuronide (pmol/min/mg)b | 8.4 ± 2.1 | 0.36 ± 0.14 | 50.8 ± 9.5* | 0.62 ± 0.26 | 21.0 ± 5.6* | 0.72 ± 0.46 |
| Ethinyl estradiol-17β-glucuronide (pmol/min/mg)c | 3.1 ± 1.3 | 25.9 ± 7.5* | 8.2 ± 2.2* | |||
| 6β-hydroxytestosterone (fold increased) | 8.5 | 43.0 | ||||
| Ethinylestradiol-3-O-glucuronide (fold increase) | 6.0 | 1.7 | 2.5 | 2.0 | ||
| Ethinylestradiol-17β-glucuronide (fold increase) | 8.4 | 2.6 | ||||
↵ a Formation of 6β-hydroxytestosterone was used as an index of CYP3A activity.
↵ b Formation of ethinylestradiol-3-O-glucuronide and ethinylestradiol-17β-glucuronide were used as an index of UGT activity.
↵ c N.A. represents no activity.
↵ d Fold increase refers to the effect of the treatments on CYP3A or UGT activity relative to the control activity.
↵* P < 0.05 compared with control.