Percentage of remaining P450 activity observed in HLMs after a 30-min preincubation with either 1 mM 1-ABT or selected concentration of a specific positive control P450 TDI, or competitive inhibitor
Concentrations of 1-ABT and selected TDI and competitive inhibitor controls represent that used in the primary incubation. Data are presented as mean (S.D.) from triplicate determinations.
Probe Reaction | 1-ABT (1 mM) Preincubation | Positive Control TDI | Competitive Inhibitor | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Preincubation | Preincubation | |||||||||||||
| P450 | 0 min | 30 min | 0 min | 30 min | 0 min | 30 min | ||||||||
| Phenacetin O-deethylase | 1A2 | 91 (2.0) | 28 (3.0) | Furafylline (10 μM) | 87 (1.5) | 16 (0.8) | α-Naphthoflavone (1 μM) | 16 (0.8) | 24 (3.3) | |||||
| Coumarin 7-hydroxylase | 2A6 | 22 (4.0) | 2.3 (0.1) | 8-Methoxypsoralen (0.5 μM) | 60 (2.7) | 13 (1.5) | Tranylcypromine (20 μM) | 40 (2.0) | 53 (6.3) | |||||
| Bupropion hydroxylase | 2B6 | 80 (3.4) | 30 (1.7) | Ticlopidine (20 μM) | 50 (3.4) | 11 (0.1) | Clotrimazole (10 μM) | 52 (8.0) | 90 (1.6) | |||||
| Taxol 6α-hydroxylase | 2C8 | 71 (0.3) | 37 (2.6) | Amiodarone (100 μM) | 35 (3.6) | 16 (3.3) | Montelukast (1 μM) | 25 (1.5) | 31 (0.8) | |||||
| Diclofenac 4′-hydroxylase | 2C9 | 90 (12) | 58 (4.2) | Tienilic Acid (20 μM) | 53 (11) | 11 (1.2) | Sulfaphenazole (10 μM) | 22 (2.6) | 27 (1.5) | |||||
| (S)-Mephenytoin 4′-hydroxylase | 2C19 | 52 (11) | 19 (1.4) | Ticlopidine (25 μM) | 65 (1.3) | 16 (4.6) | N-Benzyl Nirvanol (10 μM) | 45 (7.6) | 50 (5.8) | |||||
| Dextromethorphan O-demethylase | 2D6 | 75 (11) | 29 (2.5) | Paroxetine (20 μM) | 29 (1.2) | 5 (1.2) | Quinidine (1 μM) | 53 (5.6) | 58 (3.2) | |||||
| Chlorzoxazone 6-hydroxylase | 2E1 | 53 (4.0) | 25 (2.9) | Diethyldithiocarbamate (10 μM) | 93 (7.8) | 60 (5.6) | Tranylcypromine (10 μM) | 60 (6.7) | 71 (6.3) | |||||
| Midazolam 1′-hydroxylase | 3A4 | 26 (0.8) | 1.7 (0.3) | Erythromycin (200 μM) | 92 (1.9) | 52 (2.9) | Ketoconazole (1 μM) | 41 (1.3) | 32 (1.9) | |||||