Comparison of tolerance development and ethanol reversal of various opioid compounds

ED50 values and 95% confidence limits were calculated under acute, chronic, and chronic + ethanol conditions in mice. All opioids tested produced antinociceptive tolerance when repeatedly administered subcutaneously. Oxycodone and hydrocodone were also evaluated for oral antinociceptive potencies and tolerance development. Only oral oxycodone produced significant tolerance to itself after repeated administration.

Morphine s.c.Oxycodone s.c.Oxycodone POHydrocodone s.c.Hydrocodone PO
Acute ED504.80 (2.5–5.7)0.89 (0.72–1.12)8.29 (6.12–11.52)3.92 (3.26–4.71)38.79 (29.21–51.53)
Chronic ED5019.90* (14.8–29.1)1.70* (1.42–2.03)33.41* (25.50–44.17)9.01* (6.44–12.62)55.92 (40.63–76.96)
Chronic + ethanol ED505.20 (4.9–5.5)1.02 (0.77–1.37)35.52 (20.19–59.03)4.73 (3.51–6.38)N/A
  • N/A, not assessed.

  • * Significant shift from acute ED50 values, determined by confidence limits that no longer overlap.