Fig. 5. (Top ) Median percentage change (solid line) and corresponding interquartile range (dashed lines) of the pain tolerance versus time observed in 12 volunteers receiving sustained-release hydromorphone (SRH; 8, 16, and 32 mg), immediate-release hydromorphone (IRH; 8 mg), and placebo, respectively. Administration of 16 and 32 mg sustained-release hydromorphone resulted in a significant overall analgesic response if compared with placebo (#). An asterisk indicates times when measured analgesic response was significantly increased from baseline measurements. (Bottom ) Mean (± SD) plasma concentration versus time after administration of 8, 16, and 32 mg sustained-release hydromorphone and the mean (± SD) effect site concentration versus time after administration of 8 mg immediate-release hydromorphone.