Table 1.

Group Mean ED₅₀ Values (95% CL) in Micrograms Per Kilogram and Fold Shift Relative to Baseline for Thermal Antinociception of Methadone, Heroin, Fentanyl, and a 1:27 Fentanyl/Heroin Mixture in Male and Female Rats of Cohort 1 (n = 3 Male, 3 Female)^a

Methadone			Heroin			Fentanyl			1:27 Fentanyl/Heroin
Condition	µg/kg ED50 (95% CL)	Fold Change	Condition	µg/kg ED50 (95% CL)	Fold Change	Condition	µg/kg ED50 (95% CL)	Fold Change	Condition	*µg/kg ED50 (95% CL)	Fold Change
Baseline	896 (431–1320)		Baseline	129 (67–177))		Baseline	3.7 (2.0–5.2)		Baseline	2.7 (1.2–4.0)
Naltrexone (0.032 mg/kg/h)	>11687 (4981–18708)	>13	Naltrexone (0.032 mg/kg/h)	2665 (1722–3536)	25.6	Naltrexone (0.032 mg/kg/h)	81.3 (41–124)	20.5	Naltrexone(0.032 mg/kg/h)	42.1 (29–56)	25.7
Day 1	487 (225–705)	0.6	Day 5	104 (60–138)	1.0	Day 7	11.3 (5.0–17)	3.4	Day 12	3.6 (2.5–4.7)	1.8
Day 14	775 (399–1103)	1.0	Day19	149 (95–192)	1.4	Day 21	39.6 (23–55)	13.5	Day 26	6.8 (4.2–9.1)	3.4
Day 28	1738 (800–2360)	2.7	Day 33	159 (100–205)	1.5	Day 35	37.9 (16–59)	11.9	Day 40	7.2 (3.4–10.3)	3.3
Day 42	837 (325–1243)	1.7	Day 47	142 (106–176)	1.4	Day 49	52.9 (44–62)	19.7	Day 54	14.9 (7.4–20)	7.5
Day 56	611 (317–888)	0.7	Day 61	200 (116–271)	1.8	Day 63	72.4 (30–104)	19.1	Day 68	10.3 (7.2–13)	4.9
Day 70	1117 (597–1601)	1.6	Day 75	269 (168–357)	2.5	Day 77	63.9 (38–86)	20.2	Day 82	12.8 (4.9–18)	5.1
Day 84	959 (632–1257)	1.3	Day 89	461 (214–670)	4.6	Day 91	85.1 (41–119)	27.1	Day 96	6.3 (2.7–9.1)	2.4
Day 98	974 (502–1404)	1.3	Day 103	329 (158–492)	2.9	Day 105	42.0 (20–63)	11.4	*ED50 reflects fentanyl dose

^aBolded and underlined conditions indicate that 95% confidence limits of ED₅₀ values did not overlap with those of baseline conditions for a given opioid.

^bED₅₀ reflects fentanyl dose