Figure 5.

Influence of cyclosporine on intravenous methadone effects and pharmacodynamics. Effects were evaluated using dark-adapted pupil diameter and response to thermal stimulus. Time is relative to the start of the methadone infusion. The 2 hr cyclosporine infusion (−1 to 1 hr) was started 1 hr before methadone (0 to 1 hr). Open and solid symbols reflect controls and cyclosporine-treated subjects, respectively. (A) Miosis (time-specific pupil diameter minus pre-drug pupil diameter) versus time after start of infusion. Results are the mean ± standard deviation (N=12). (B) Miosis versus plasma R-methadone concentrations. Results are the mean (SD omitted for clarity, N=12). (C) Maximally tolerated temperature difference compared to pre-drug baseline using the methods of limits over the first 5 hr after the start of the methadone infusion. Results are the averages of differences (standard deviation omitted for clarity, N=11, asterisks denote significant differences vs baseline). (D) Stimulus-response relationship (verbal analog scale pain ratings) in response to discreet thermal stimuli, at the end of the 1 hr methadone infusion, and the influence of cyclosporine. Results are the mean (standard deviation omitted for clarity, N=12). (E) Pain ratings (verbal analog scale) in response to thermal stimulus (shown for 44.8 and 46.5 °C). Results are the mean (standard deviation omitted for clarity, N=12).