Treatment | Concentration | Enzyme Activitya | |||||
---|---|---|---|---|---|---|---|
CYP1A2 | CYP2B6 | CYP2C8 | CYP2C9 | CYP2C19 | CYP3A4/5 | ||
pmol/mg of microsomal protein/min | |||||||
DMSO | 0.1% (v/v) | 63.5 ± 50.8 | 65.9 ± 34.4 | 236 ± 73 | 928 ± 320 | 6.41 ± 4.45 | 2980 ± 1040 |
Milnacipran | 3 μM | 64.6 ± 50.1 | 76.1 ± 48.9 | 259 ± 124 | 979 ± 348 | 6.25 ± 3.71 | 3470 ± 480 |
Milnacipran | 10 μM | 72.1 ± 56.1 | 111 ± 61 | 276 ± 81 | 997 ± 305 | 6.45 ± 3.44 | 4700 ± 540 |
Milnacipran | 30 μM | 73.4 ± 59.4 | 168 ± 90* | 285 ± 74 | 1010 ± 280 | 5.80 ± 3.08 | 5840 ± 580 |
Omeprazole | 100 μM | 1630 ± 750† | 419 ± 214† | 904 ± 483 | 1320 ± 650 | 8.27 ± 6.30 | 4100 ± 2280 |
Phenobarbital | 750 μM | 124 ± 69 | 666 ± 399† | 959 ± 257† | 1680 ± 650† | 20.8 ± 17.0 | 11,400 ± 1300†† |
Rifampin | 10 μM | 114 ± 86 | 388 ± 262† | 1130 ± 250† | 1930 ± 570† | 43.7 ± 33.1†† | 11,500 ± 1000†† |
↵a Values (rounded to three significant figures) are the mean ± S.D. (rounded to the same degree of accuracy) of three determinations (i.e., three human hepatocyte preparations). CYP1A2, phenacetin O-dealkylation; CYP2B6, bupropion hydroxylation; CYP2C8, amodiaquine N-dealkylation; CYP2C9, diclofenac 4′-hydroxylation; CYP2C19, S-mephenytoin 4′-hydroxylation; CYP3A4/5, testosterone 6β-hydroxylation.
↵* Significantly different from the vehicle control (DMSO) according to Dunnett's method (p < 0.05) when the positive control groups (omeprazole, phenobarbital, and rifampin) were excluded from the statistical analysis.
↵† Statistical significance found among the treatment groups according to Kruskal-Wallis one-way analysis on ranks (p < 0.05) and Dunnett's method when the positive control groups (omeprazole, phenobarbital, and rifampin) were included in the statistical analysis.
↵†† Significantly different from the vehicle control (DMSO) according to the Dunnett's method (p < 0.05) when the positive control groups (omeprazole, phenobarbital, and rifampin) were included in the statistical analysis.