Table 1 Mean ± SD plasma concentrations of (A) morphine, (B) morphine-6-glucuronide (M6G) and (C) morphine-3-glucuronide (M3G) following a single oral administration of codeine (0.3, 0.6, 1.2 mg/kg) or intravenous administration of morphine (0.2 mg/kg) to 7 horses

Time (h)

0.3 mg/kg PO

0.6 mg/kg PO

1.2 mg/kg PO

0.2 mg/kg IV

0

ND

ND

ND

ND

0.08

ND^d

ND^d

ND^d

117.4 ± 12.7^,b,c

0.16

ND

0.68 ± 0.22^d

0.76 ± 0.52^d

72.0 ± 9.76^a,b,c

0.25

0.56 ± 0^d

1.02 ± 0.83^d

1.56 ± 1.17^d

53.9 ± 7.23^a,b,c

0.5

0.72 ± 0.51^d

0.97 ± 0.45^d

2.28 ± 1.71^d

34.2 ± 3.91^a,b,c

0.75

0.81 ± 0.38^d

1.13 ± 0.36^d

1.87 ± 1.24^d

25.5 ± 3.34^a,b,c

1.0

0.77 ± 0.26^d

0.99 ± 0.39^d

1.66 ± 0.80^d

21.2 ± 3.35^a,b,c

2.0

0.75 ± 0.19^d

1.02 ± 0.27^d

1.81 ± 0.99^d

12.5 ± 2.09^a,b,c

3.0

0.97 ± 0.25^d

1.61 ± 0.44^d

2.08 ± 0.86^d

7.02 ± 1.28^a,b,c

4.0

1.08 ± 0.25^d

1.73 ± 0.61^d

2.34 ± 0.84^d

4.79 ± 0.88^a,b,c

5.0

1.10 ± 0.21^c,d

1.75 ± 0.40^d

2.57 ± 0.90^a

3.62 ± 0.59^a,b

6.0

1.15 ± 0.34^c,d

1.82 ± 0.47

2.88 ± 0.96^a

2.56 ± 0.49^a

8.0

1.16 ± 0.29^c

1.64 ± 0.37^d

2.84 ± 0.78^a,b,d

1.49 ± 0.27^c

12.0

0.80 ± 0.20^b,c

1.54 ± 0.47^a,c,d

2.35 ± 0.71^a,b,d

0.76 ± 0.11^b,c

18.0

0.60 ± 0.22^b,c

1.09 ± 0.41^a,c,d

2.02 ± 0.61^a,b,d

0.46 ± 0.08^b,c

24.0

0.67 ± 0.20^b,c

0.88 ± 0.43^a,d

1.68 ± 0.80^a,d

0.43 ± 0.0^b,c

36.0

0.39 ± 0^c

0.56 ± 0.25^c

0.67 ± 0.26^a,b,d

ND^c

48.0

ND

ND

0.66 ± 0.21

ND

72.0

ND

ND

ND

ND

Morphine

Time (h)

0.3 mg/kg PO

0.6 mg/kg PO

1.2 mg/kg PO

0.2 mg/kg IV

0

ND

ND

ND

ND

0.08

ND^d

ND^d

ND^d

12.6 ± 2.31^a,b,c

0.16

0.25 ± 0.02^d

0.97 ± 0.78^d

0.92 ± 1.14^d

15.9 ± 2.10^a,b,c

0.25

0.38 ± 0.22^c,d

2.10 ± 3.04d

3.90 ± 4.48^d

14.3 ± 3.27^a,b,c

0.5

4.05 ± 2.84^c,d

7.94 ± 8.22

18.3 ± 12.7^a

12.4 ± 2.56^a

0.75

6.93 ± 2.94^c

10.5 ± 5.26

21.6 ± 13.3^a

10.8 ± 2.15

1.0

8.25 ± 2.45^c

10.7 ± 3.69^c

20.7 ± 12.0^a,c,d

9.77 ± 2.02^c

2.0

8.13 ± 2.21^c

10.3 ± 2.44^c

19.4 ± 9.90^a,b,d

6.14 ± 1.43^c

3.0

8.19 ± 2.49^c,d

10.9 ± 3.84^c,d

17.8 ± 4.87^a,b,d

4.27 ± 0.88^a,b,c

4.0

6.43 ± 1.71^c,d

8.83 ± 3.00^c,d

14.9 ± 5.56^a,b,d

3.43 ± 0.57^a,b,c

5.0

5.07 ± 1.28^b,c,d

7.78 ± 2.77^a,c,d

12.2 ± 2.98^a,b,d

3.06 ± 0.41^a,b,c

6.0

4.46 ± 1.33^b,c

7.28 ± 2,79^a,c,d

11.3 ± 3.43^a,b,d

2.69 ± 0.43^b,c

8.0

4.12 ± 1.91^c

5.38 ± 2.21^c,d

10.0 ± 4.54^a,b,d

2.08 ± 0.47^b,c

12.0

2.04 ± 0.75^b,c

5.08 ± 4.06^a,c,d

7.71 ± 5.16^a,d

1.13 ± 0.34^b,c

18.0

1.12 ± 0.69^c

1.96 ± 1.08^c,d

5.10 ± 3.88^a,b,d

0.53 ± 0.18^b,c

24.0

0.75 ± 0.47^c

1.25 ± 0.77^c,d

3.32 ± 2.73^a,b,d

0.32 ± 0.10^b,c

36.0

0.35 ± 0.17_c

0.42 ± 0.36^c

1.25 ± 1.26^a,b,d

0.15 ± 0.03^c

48.0

0.27 ± 0.05

0.28 ± 0.11

0.60 ± 0.58^d

ND^c

72.0

ND

ND

0.22 ± 0.09^d

ND^c

Morphine

Time (h)

0.3 mg/kg PO

0.6 mg/kg PO

1.2 mg/kg PO

0.2 mg/kg IV

0

ND

ND

ND

ND

0.08

0.14 ± 0.02^d

0.20 ± 0.09^d

0.16 ± 0.04d

242.8 ± 74.3^a,b,c

0.16

0.46 ± 0.24^d

5.83 ± 9.74^d

5.09 ± 8.13^d

324.3 ± 73.6^a,b,c

0.25

3.46 ± 2.24^d

44.9 ± 81.6^d

63.4 ± 85.2^d

319.8 ± 63.4^a,b,c

0.5

65.0 ± 70.4^c,d

196.9 ± 263.0

422.3 ± 374.9^a

291.3 ± 51.6^a

0.75

119.7 ± 61.6^c

265.5 ± 194.6

505.5 ± 413.0^a

266.4 ± 40.1

1.0

144.63 ± 47.2^c

265.3 ± 141.4

493.6 ± 255.4^a

255.1 ± 33.4

2.0

170.7 ± 47.9^c

284.9 ± 136.3^c

499.1 ± 310.1^a,b,d

181.0 ± 21.7^c

3.0

188.1 ± 68.0^b,c

303.3 ± 108.2^a,c,d

490.1 ± 207.4^a,b,d

131.9 ± 18.3^b,c

4.0

161.4 ± 50.7^b,c

266.5 ± 95.5^a,c,d

418.3 ± 143.1^a,b,d

103.0 ± 16.3^b,c

5.0

126.7 ± 39.0^c

236.4 ± 78.2^a,c,d

357.6 ± 118.8^a,b,d

85.0 ± 17.7^b,c

6.0

110.6 ± 42.2^b,c

224.0 ± 85.7^a,c,d

329.5 ± 121.9^a,c,d

73.6 ± 12.7^b,c

8.0

96.5 ± 42.4^b,c

161.8 ± 64.4^a,c,d

287.6 ± 140.1^a,b,d

52.9 ± 10.5^b,c

12.0

48.6 ± 20.0^b,c

144.3 ± 90.2^a,d

223.2 ± 126.3^a,d

26.0 ± 4.98^b,c

18.0

26.43 ± 18.0^b,c

53.9 ± 25.6^a,c,d

146.5 ± 83.0^a,b,d

11.7 ± 2.58^b,c

24.0

19.7 ± 14.6^c

36.8 ± 19.0^c,d

100.0 ± 67.2^a,b,d

7.60 ± 2.81^b,c

36.0

4.67 ± 4.23^c

8.87 ± 7.17^c,d

28.2 ± 20.0^a,b,d

2.08 ± 1.27^b,c

48.0

1.47 ± 1.20^c

2.39 ± 1.52^c

10.2 ± 10.1^a,b,d

0.81 ± 0.54^c

72.0

0.31 ± 0.19^c

0.47 ± 0.28^c

1.05 ± 0.71^a,b,d

0.24 ± 0.10^c