Table 2.
Experimentally measured in vitro clearance of oxycodone and reported CYP3A4 and CYP2D6 activities in hepatocyte batches used in the study.
| Donor age | 3 days | 2 months | 5 months | 4 years | Adult pool |
|---|---|---|---|---|---|
| Supplier | BD Biosciences | Invitrogen | BD Biosciences | BD Biosciences | Celsis |
| In vitro CLu | 9.8 | 2.2 | 0.9 | 2.1 | 4.2 |
| Activity vs. adult batch | 2.3 | 0.5 | 0.2 | 0.5 | 1.0 |
| CYP3A4 activity1 | 790 | 212 | 63 | 310 | 210–2802 |
| Activity vs. adult batch | 3.2 | 0.9 | 0.3 | 1.3 | 1.03 |
| CYP2D6 activity4 | 15 | – | 6.7 | 30 | - |
| Activity vs. 3-day batch | 1.0 | 0.4 | 2.0 | ||
| CYP2D6 activity5 | 29 | 15.5 | |||
| Activity vs. adult batch | 1.9 | 1.0 |
In vitro CLu (μl/min/106 cells) obtained from the incubation with 1 μM oxycodone, except for the 5-month batch from 10 μM oxycodone. All the CYP activities were provided by the supplier in pmol/(min*106 cells): 16β-hydroxytestosterone formation using 200 μM testosterone; 2estimated range for incubation with 200 μM testosterone was calculated by multiplying the supplier value (161) obtained with 50 μM testosterone (60 min) by 1.3–1.75 based on the Hill equations constants (S50 = 25–50 μM; n = 1.45; Kenworthy et al., 2001; Brown et al., 2007); 3normalised using average value of 245; 41′-hydroxybufuralol formation using 25 μM bufuralol; 5dextrorphan formation using 15 μM dextromethorphan (2 month) or 8 μM dextromethorphan (adult).