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Table 3 Pharmacokinetic values (mean ± SD) for codeine and codeine 6-glucuronide (C6G), morphine, morphine 3-glucuronide (M3G), and morphine 6-glucuronide (M6G) after a single oral administration of codeine (0.6 mg/kg) to horses. Parameters are sorted by predicted phenotypic groups

From: Functional phenotyping of the CYP2D6 probe drug codeine in the horse

Parameter

Predicted phenotype

Poor (n = 11)

Extensive (n = 72)

Ultra-rapid (n = 17)

Codeine AUC0-∞ (h·ng/mL)

257.72 ± 122.93b,c

76.49 ± 46.35a,c

20.84 ± 6.33a,b

C6G AUC0-∞ (h·ng/mL)

500.15 ± 249.83

630.12 ± 331.76

523.38 ± 209.18

Morphine AUC0-∞ (h·ng/mL)

27.46 ± 9.14

30.82 ± 10.26

34.66 ± 6.31

M3G AUC0-∞ (h·ng/mL)

2700.64 ± 892.03c

3277.89 ± 935.74

3904.93 ± 987.01a

M6G AUC0-∞ (h·ng/mL)

98.25 ± 32.76b,c

170.32 ± 71.02a

180.92 ± 65.70a

MR O-demethylation

0.089 ± 0.027b,c

0.022 ± 0.011a,c

0.0095 ± 0.001a,b

MR glucuronidation

0.711 ± 0.596b,c

0.153 ± 0.137a

0.045 ± 0.020a

Codeine t1/2d (h)

1.32 ± 0.56

2.50 ± 1.37

2.24 ± 0.88

  1. MR for O-demethylation calculated as: (codeine AUC)/(morphine AUC + M3G AUC + M6G AUC)
  2. MR for glucuronidation calculated as: (codeine AUC)/(codeine-6-glucuronide AUC)
  3. AUC area under the plasma concentration-time curve, MR metabolic ratio, t1/2 terminal half-life
  4. asignificantly different than poor metabolizers (P < 0.05); bsignificantly different than extensive metabolizers (P < 0.05); csignificantly different than ultra-rapid metabolizers (P < 0.05)
  5. dexpressed as a harmonic mean