Percentage of control activities for hydroxylinezolid, M1, formation in the presence of various substrates and inhibitors selective for individual CYP enzymes
| CYP Enzyme | Inhibitor (μM) | % Control for M1 Formation |
|---|---|---|
| CYP1A2 | ANF (50) | 89.64 ± 5.901-a |
| CYP2A6 | COUM (50) | 72.02 ± 4.32 |
| CYP2B6 | ORPH (50) | 108.03 ± 25.34 |
| CYP2C8 | RETN (50) | 82.67 ± 6.49 |
| CYP2C9 | SULF (10) | 103.21 ± 3.86 |
| CYP2C19 | MEPH (250) | 93.26 ± 1.21 |
| CYP2D6 | QUIN (5) | 84.40 ± 6.13 |
| CYP2E1 | pNITR (100) | 90.48 ± 3.39 |
| CYP3A4 | KETO (5) | 91.07 ± 6.35 |
| CYP4A11 | LAUR (50) | 92.13 ± 5.37 |
CYP enzyme-selective compounds were used to study their inhibitory effects on the oxidation of linezolid (100 μM) in human liver microsomes. The P-450 selective inhibitors substrates used in this experiment were: 50 μM α-naphthoflavone (CYP1A2, Chang et al., 1994); 50 μM coumarin (CYP2A6, Pearce et al., 1992); 50 μM orphenadrine (CYP2B6, Stevens et al., 1997); 50 μM retinoic acid (CYP2C8, Yamazaki and Shimada, 1999); 10 μM sulfaphenazole (CYP2C9,Newton et al., 1995); 250 μM (S)-mephenytoin (CYP2C19,Wrighton et al., 1993); 5 μM quinidine (CYP2D6, Guengerich et al., 1986); 100 μM para-nitrophenol (CYP2E1, Tassaneeyakul et al., 1993); 5 μM ketoconazole (CYP3A4, Gibbs et al., 1999); 50 μM lauric acid (CYP4A11, Clarke et al., 1994). Incubation conditions were carried out as described under Experimental Procedures. Each data point represents the mean (±S.D.) of triplicate determinations.
↵1-a Mean ± S.D.