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Time course of pupil diameter over 12 hours (3A) in 16 healthy human subjects following a 2.5 μg/kg intravenous infusion of fentanyl and hysteresis plots (3B, 3C) of mean change in pupil diameter versus mean plasma fentanyl concentration in the order of time on the pre- (closed symbol) and post- (open symbol) treatment days in the placebo (blue squares) and St. John’s wort (red circles) groups.
