Table 3.
Diacetylmorphine (DAM) and morphine absorption: comparison of pharmacokinetic parameters for morphine and its glucuronides after oral diacetylmophine-d3 and morphine-d3 administration
| Opioid-dependent patients | Opioid-naive volunteers | Dependent vs. naive | ||||||
|---|---|---|---|---|---|---|---|---|
| DAM-d3 | Morphine-d3 | DAM vs. morphine | DAM-d3 | morphine-d3 | DAM vs. morphine | DAM-d3 | morphine-d3 | |
| Dose (µmol) | 48.5 | 48.5 | 48.5 | 48.5 | ||||
| DAM-d3 AUC (µmol h l−1) | <l.d. | <l.d. | ||||||
| MAM-d3 AUC (µmol h l−1) | <l.d. | <l.d. | ||||||
| Morphine-d3 | ||||||||
| AUC (µmol h l−1) | 0.22 ± 0.06 | 0.18 ± 0.07 | 0.12 ± 0.05 | 0.12 ± 0.06 | ||||
| Cmax (µmol l−1) | 0.26 ± 0.06 | 0.14 ± 0.11 | P = 0.0173 | 0.10 ± 0.08 | 0.06 ± 0.05 | P = 0.014 | P = 0.0046 | P = 0.046 |
| tmax (min) | 9 ± 2 | 20 ± 11 | P = 0.0418 | 20 ± 14 | 36 ± 38 | P = 0.484 | P = 0.0423 | P = 0.560 |
| F (%) | 45.6 ± 8.1 | 37.2 ± 10.2 | P = 0.0499 | 22.9 ± 9.3 | 23.9 ± 10.6 | P = 0.327 | P = 0.0011 | P = 0.0209 |
| Morphine-d3-3-glucuronide | ||||||||
| AUC (µmol h l−1) | 2.83 ± 0.78 | 2.87 ± 0.72 | 2.56 ± 0.73 | 2.29 ± 1.04 | ||||
| Morphine-d3-6-glucuronide | ||||||||
| AUC (µmol h l−1) | 0.62 ± 0.28 | 0.55 ± 0.17 | 0.53 ± 0.18 | 0.6 ± 0.26 | ||||
| RatioG/N | 15.7 ± 3.7 | 19.7 ± 4.3 | p = 0.0117 | 31.3 ± 18.11 | 29.9 ± 17.5 | P = 0.7794 | P = 0.0357 | P = 0.207 |
<l.d., below limit of detection, P-values were calculated using Mann–Whitney U-test or Wilcoxon's matched-pairs test, respectively; n = 8 per group.