Enzyme | Substrate | Marker Metabolite | Cell Culture Model | Mean Specific Activity ± S.D. | Mean Statistical Difference HepaRG versus SC-PHH | Mean Difference (>2-fold) HepaRG versus SC-PHH Median | PHH Suspension Median Specific Activities |
---|---|---|---|---|---|---|---|
pmol/min-million cells | pmol/min-million cells | ||||||
CYP1A2 | Phenacetin | Acetaminophen | HepaRG | 2.78 ± 0.728 | P < 0.0001 | No | 48.0 (212 donor preps) |
SC-PHH (N = 52) | 7.18 ± 7.78 | ||||||
CYP2A6 | Coumarin | 7-Hydroxycoumarin | HepaRG | 0.851 ± 0.159 | No | No | Not Available |
SC-PHH (N = 53) | 1.03 ± 0.974 | ||||||
CYP2B6 | Bupropion | Hydroxybupropion | HepaRG | 17.9 ± 2.21 | P < 0.0001 | Yes, 8.3X | 32.1 (137 donor preps) |
SC-PHH (N = 52) | 2.94 ± 2.78 | ||||||
CYP2C8 | Paclitaxel | 6α-Hydroxypaclitaxel | HepaRG | 0.223 ± 0.035 | No | No | 5.24 (149 donor preps) |
SC-PHH (N = 34) | 0.517 ± 0.802 | ||||||
CYP2C9 | Diclofenac | 4′Hydroxydiclofenac | HepaRG | 3.94 ± 0.380 | No | No | 88.2 (187 donor preps) |
SC-PHH (N = 54) | 5.37 ± 9.54 | ||||||
CYP2C19 | Mephenytoin | 4′-Hydroxydiclofenac | HepaRG | 1.52 ± 0.408 | No | No | 13.8 (208 donor preps) |
SC-PHH (N = 48) | 2.26 ± 4.71 | ||||||
CYP2D6 | Dextromethorphan | Dextrorphan | HepaRG | 0.401 ± 0.0622 | No, P = 0.057 | No | 21.1 (24 donor preps) |
SC-PHH (N = 36) | 1.18 ± 1.70 | ||||||
CYP3A4/5 | Testosterone | 6β-Hydroxytestosterone | HepaRG | 248 ± 50.9 | P < 0.0001 | Yes, 6.8X | 407 (195 donor preps) |
SC-PHH (N = 52) | 55.2 ± 49.4 | ||||||
CYP3A4/5 | Midazolam | 1-Hydroxymidazolam | HepaRG | 28.4 ± 2.39 | NA | NA | 63.7 (132 donor preps) |
SC-PHH (N = 0) | Not available | ||||||
FMO | Benzydamine | Benzydamine N-oxide | HepaRG | 17.3 ± 1.74 | NA | NA | 144 (105 donor preps) |
SC-PHH (N = 0) | Not available | ||||||
UGT | 7-Hydroxycoumarin | 7-Hydroxycoumarin glucuronide | HepaRG | 346 ± 49.7 | NA | NA | 494 (196 donor preps) |
SC-PHH (N = 0) | Not available | ||||||
SULT | 7-Hydroxycoumarin | 7-Hydroxycoumarin sulfate | HepaRG | 9.23 ± 2.92 | NA | NA | 37 (195 donor preps) |
SC-PHH (N = 0) | Not available |
NA, Data from SC-PHH not available.