| Disease | TWELVE HEALTHY SUBJECTS (5 FEMALE, 7 MALE) COMPLETED THIS 3-PERIOD, OPEN-LABEL, FIXED SCHEDULE STUDY. TOLBUTAMIDE (CYP2C9), CAFFEINE (CYP1A2), DEXTROMETHORPHAN (CYP2D6), ORAL MIDAZOLAM, (INTESTINAL WALL AND HEPATIC CYP2C9), AND INTRAVENOUS
MIDAZOLAM (HEPATIC CYP3A) WERE ADMINISTERED BEFORE, WITH SHORT-TERM ST JOHN'S WORT DOSING (900 MG), AND AFTER 2 WEEKS OF INTAKE (300 MG 3 TIMES A DAY) TO DETERMINE CYP ACTIVITIES. LONG TERM ST JOHN'S WORT ADMINISTRATION RESULTED IN A SIGNIFICANT
AND SELECTIVE INDUCTION OF CYP3A ACTIVITY IN THE INTESTINAL WALL. ST JOHN'S WORT DID NOT ALTER THE CYP2C9, CYP1A2, OR CYP2D6 ACTIVITIES. REDUCED THERAPEUTIC EFFICACY OF DRUGS METABOLIZED BY CYP3A SHOULD BE ANTICIPATED DURING LONG-TERM
ADMINISTRATION OF ST JOHN'S WORTT. |