Table 3

In vitro intrinsic clearance values and fraction unbound in the incubation conditions for 29 drugs examined

DrugMicrosomal ConcentrationIn VitroT1/2CL′intfu(mic)
mg/ml min ml/min/kg
Basic compounds
 Chlorpromazine1.025  ± 625  ± 60.11  ± 0.02
 Propafenone0.58.0  ± 0.4166  ± 80.26  ± 0.04
 Verapamil0.510  ± 0.2122  ± 20.43  ± 0.10
 Diphenhydramine6.049  ± 242.1  ± 0.90.29  ± 0.02
 Lorcainide1.013  ± 250  ± 60.52  ± 0.03
 Diltiazem2.021  ± 315  ± 20.76  ± 0.10
 Amitriptyline0.592  ± 1314  ± 20.15  ± 0.04
 Desipramine0.574  ± 2417  ± 70.21  ± 0.01
 Imipramine0.566  ± 519  ± 20.18  ± 0.04
 Ketamine1.023  ± 327  ± 40.49  ± 0.02
 Quinidine5.037  ± 53.4  ± 0.50.32  ± 0.17
 Clozapine5.027  ± 54.6  ± 0.90.13  ± 0.01
Neutral compounds
 Dexamethasone5.042  ± 33.0  ± 0.21.00  ± 0.07
 Prednisone5.047  ± 12.7  ± 0.00.20  ± 0.02
 Diazepam5.054  ± 192.3  ± 0.70.28  ± 0.05
 Midazolam1.03.9  ± 0.1160  ± 30.88  ± 0.12
 Methoxsalen0.531  ± 340  ± 30.94  ± 0.11
 Alprazolam5.0105  ± 661.6  ± 1.00.66  ± 0.04
 Triazolam1.033  ± 219  ± 10.78  ± 0.09
 Zolpidem5.044  ± 52.8  ± 0.30.58  ± 0.10
Acidic compounds
 Diclofenac0.311  ± 3189  ± 391.00  ± 0.13
 Ibuprofen2.036  ± 48.8  ± 0.90.84  ± 0.13
 Tolbutamide1071  ± 120.90  ± 0.150.95  ± 0.03
 Warfarin10>120<0.520.47  ± 0.05
 Tenidap3.026  ± 28.3  ± 0.70.32  ± 0.01
 Tenoxicam1038  ± 111.7  ± 0.40.78  ± 0.03
 Amobarbital1066  ± 50.94  ± 0.070.76  ± 0.08
 Hexobarbital5.048  ± 62.3  ± 0.30.81  ± 0.05
 Methohexital1.013  ± 249  ± 80.86  ± 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.