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.