TABLE 3.
Expected additive ED50 values (Zadd), actual (experimentally determined) ED50 values (Zmix), and the ratio of expected/actual ED50 values for drug mixtures for antinociception and operant responding in rats
| Mixture | Zadd (95% CL) | Zmix (95% CL) |
|---|---|---|
| Mechanical nociception test | ||
| 1:3 2-BFI/fentanyl | 1.78 (1.43, 2.21) | 1.19 (0.90, 1.58) |
| 1:1 2-BFI/fentanyl | 3.54 (2.86, 4.40) | 2.62 (2.05, 3.36) |
| 3:1 2-BFI/fentanyl | 5.31 (4.28, 6.58) | 3.80 (2.77, 5.21) |
| 1:3 2-BFI/buprenorphine | 7.10 (5.73, 8.81) | 1.42 (0.94, 2.13)a |
| 1:1 2-BFI/buprenorphine | 7.09 (5.72, 8.78) | 1.88 (1.25, 2.84)a |
| 3:1 2-BFI/buprenorphine | 7.08 (5.71, 8.77) | 6.50 (4.19, 10.08) |
| 1:3 2-BFI/NAQ | 31.70 (25.57, 39.29) | 4.95 (3.66, 6.71)a |
| 1:1 2-BFI/NAQ | 15.29 (12.33, 18.95) | 3.32 (2.59, 4.24)a |
| 3:1 2-BFI/NAQ | 9.81 (7.92, 12.16) | 5.23 (3.62, 7.56)a |
| Thermal nociception test | ||
| 1:3 2-BFI/fentanyl | 2.52 (1.92, 3.30) | 4.05 (3.28, 5.01)b |
| 1:1 2-BFI/fentanyl | 5.01 (3.81, 6.58) | 7.62 (6.50, 8.95)b |
| 3:1 2-BFI/fentanyl | 7.50 (5.71, 9.85) | 8.83 (7.12, 10.96) |
| 1:3 2-BFI/buprenorphine | 2.51 (1.90, 3.31) | 5.19 (3.18, 8.48) |
| 1:1 2-BFI/buprenorphine | 5.00 (3.80, 6.58) | 8.16 (4.99, 13.35) |
| 3:1 2-BFI/buprenorphine | 7.49 (5.70, 9.85) | 12.23 (9.41, 15.91) |
| 1:3 2-BFI/NAQ | 44.77 (34.08, 58.83) | 11.07 (6.60, 18.59)a |
| 1:1 2-BFI/NAQ | 21.57 (16.42, 28.34) | 11.28 (6.26, 20.33) |
| 3:1 2-BFI/NAQ | 13.85 (10.54, 18.20) | 11.02 (6.36, 19.10) |
| Operant responding | ||
| Mixtures in mechanical nociception test | ||
| 1:3 2-BFI/fentanyl | 5.60 (4.67, 6.72) | 5.51 (3.87, 7.84) |
| 1:1 2-BFI/fentanyl | 7.04 (5.87, 8.43) | 5.43 (4.26, 6.95) |
| 3:1 2-BFI/fentanyl | 8.43 (7.04, 10.11) | 7.81 (6.32, 9.67) |
| 1:3 2-BFI/buprenorphine | 8.52 (7.11, 10.22) | 5.27 (3.86, 7.19) |
| 1:1 2-BFI/buprenorphine | 8.97 (7.48, 10.75) | 6.97 (5.58, 8.70) |
| 3:1 2-BFI/buprenorphine | 9.41 (7.85, 11.27) | 6.93 (5.02, 9.57) |
| 1:3 2-BFI/NAQ | 11.04 (6.62, 19.04) | 10.73 (6.77, 17.00) |
| 1:1 2-BFI/NAQ | 10.64 (7.16, 16.63) | 11.48 (8.31, 15.85) |
| 3:1 2-BFI/NAQ | 10.25 (7.69, 14.21) | 8.22 (7.34, 9.20) |
| Mixtures in thermal nociception test | ||
| 1:3 2-BFI/fentanyl | 4.28 (3.57, 5.13) | 6.28 (5.23, 7.53)b |
| 1:1 2-BFI/fentanyl | 6.13 (5.12, 7.36) | 6.08 (4.85, 7.63) |
| 3:1 2-BFI/fentanyl | 7.99 (6.67, 9.58) | 8.19 (5.94, 11.31) |
| 1:3 2-BFI/buprenorphine | 8.52 (7.11, 10.22) | 7.63 (6.40, 9.11) |
| 1:1 2-BFI/buprenorphine | 8.97 (7.48, 10.75) | 6.92 (5.12, 9.39) |
| 3:1 2-BFI/buprenorphine | 9.41 (7.85, 11.27) | 8.09 (6.50, 10.06) |
| 1:3 2-BFI/NAQ | 11.04 (6.62, 19.04) | 8.81 (5.94, 13.07) |
| 1:1 2-BFI/NAQ | 10.64 (7.16, 16.63) | 11.81 (6.91, 20.18) |
| 3:1 2-BFI/NAQ | 10.25 (7.69, 14.21) | 9.42 (7.28, 12.20) |
a
Zmix confidence limits do not overlap with Zadd confidence limits: Zmix lower than Zadd (supra-additivity).
b
Zmix confidence limits do not overlap with Zadd confidence limits: Zmix higher than Zadd (infra-additivity).