In vitro intrinsic clearance values and fraction unbound in the incubation conditions for 29 drugs examined
Drug | Microsomal Concentration | In VitroT1/2 | CL′int | fu(mic) |
---|---|---|---|---|
mg/ml | min | ml/min/kg | ||
Basic compounds | ||||
Chlorpromazine | 1.0 | 25 ± 6 | 25 ± 6 | 0.11 ± 0.02 |
Propafenone | 0.5 | 8.0 ± 0.4 | 166 ± 8 | 0.26 ± 0.04 |
Verapamil | 0.5 | 10 ± 0.2 | 122 ± 2 | 0.43 ± 0.10 |
Diphenhydramine | 6.0 | 49 ± 24 | 2.1 ± 0.9 | 0.29 ± 0.02 |
Lorcainide | 1.0 | 13 ± 2 | 50 ± 6 | 0.52 ± 0.03 |
Diltiazem | 2.0 | 21 ± 3 | 15 ± 2 | 0.76 ± 0.10 |
Amitriptyline | 0.5 | 92 ± 13 | 14 ± 2 | 0.15 ± 0.04 |
Desipramine | 0.5 | 74 ± 24 | 17 ± 7 | 0.21 ± 0.01 |
Imipramine | 0.5 | 66 ± 5 | 19 ± 2 | 0.18 ± 0.04 |
Ketamine | 1.0 | 23 ± 3 | 27 ± 4 | 0.49 ± 0.02 |
Quinidine | 5.0 | 37 ± 5 | 3.4 ± 0.5 | 0.32 ± 0.17 |
Clozapine | 5.0 | 27 ± 5 | 4.6 ± 0.9 | 0.13 ± 0.01 |
Neutral compounds | ||||
Dexamethasone | 5.0 | 42 ± 3 | 3.0 ± 0.2 | 1.00 ± 0.07 |
Prednisone | 5.0 | 47 ± 1 | 2.7 ± 0.0 | 0.20 ± 0.02 |
Diazepam | 5.0 | 54 ± 19 | 2.3 ± 0.7 | 0.28 ± 0.05 |
Midazolam | 1.0 | 3.9 ± 0.1 | 160 ± 3 | 0.88 ± 0.12 |
Methoxsalen | 0.5 | 31 ± 3 | 40 ± 3 | 0.94 ± 0.11 |
Alprazolam | 5.0 | 105 ± 66 | 1.6 ± 1.0 | 0.66 ± 0.04 |
Triazolam | 1.0 | 33 ± 2 | 19 ± 1 | 0.78 ± 0.09 |
Zolpidem | 5.0 | 44 ± 5 | 2.8 ± 0.3 | 0.58 ± 0.10 |
Acidic compounds | ||||
Diclofenac | 0.3 | 11 ± 3 | 189 ± 39 | 1.00 ± 0.13 |
Ibuprofen | 2.0 | 36 ± 4 | 8.8 ± 0.9 | 0.84 ± 0.13 |
Tolbutamide | 10 | 71 ± 12 | 0.90 ± 0.15 | 0.95 ± 0.03 |
Warfarin | 10 | >120 | <0.52 | 0.47 ± 0.05 |
Tenidap | 3.0 | 26 ± 2 | 8.3 ± 0.7 | 0.32 ± 0.01 |
Tenoxicam | 10 | 38 ± 11 | 1.7 ± 0.4 | 0.78 ± 0.03 |
Amobarbital | 10 | 66 ± 5 | 0.94 ± 0.07 | 0.76 ± 0.08 |
Hexobarbital | 5.0 | 48 ± 6 | 2.3 ± 0.3 | 0.81 ± 0.05 |
Methohexital | 1.0 | 13 ± 2 | 49 ± 8 | 0.86 ± 0.13 |
Each in vitro T1/2 and microsomal binding value represents mean ± S.D. for triplicate determinations. Intrinsic clearance values were calculated from in vitro T1/2data as described in Experimental Procedures.