Table 2

Values for systemic clearance, fraction unbound in plasma, and blood-to-plasma ratio for 29 drugs examined in this analysis

DrugFraction Unbound in Plasma (fu)Blood-to-Plasma RatioNonrenal Clearance2-aReferences
PlasmaBlood
ml/min/kg
Basic compounds
 Chlorpromazine0.050.788.62-b 11 Dahl and Strandjard, 1974; Maxwell et al., 1972; Lund, 1980
 Propafenone0.040.701319 Bryson et al., 1993
 Verapamil0.100.772-c 1519 Eichelbaum et al., 1984
 Diphenhydramine0.220.652-c 6.29.5 Blyden et al., 1986
 Lorcainide0.150.771418 Somani et al., 1987; Klotz et al., 1978
 Diltiazem0.221.01212 Echizen and Eichelbaum, 1986; Smith et al., 1983
 Amitriptyline0.050.861012 Schulz et al., 1983
 Desipramine0.180.961212 Brosen and Gram, 1988
 Imipramine0.101.11312 Sallee and Pollack, 1990; Abernathy et al., 1985
 Ketamine0.880.822-c 1620 White et al., 1985
 Quinidine0.130.922.52.7 Greenblatt et al., 1977; Rakhit et al., 1984; Hughes et al., 1975
 Clozapine0.050.872.52.9 Cheng et al., 1988
Neutral compounds
 Dexamethasone0.320.933.53.8 Tseui et al., 1979; Peterson et al., 1983
 Prednisone0.250.832-c 4.14.9 Schalm et al., 1977
 Diazepam0.0130.710.40.6 Greenblatt et al., 1980; Maguire et al., 1980
 Midazolam0.050.534.68.7 Heizmann et al., 1983
 Methoxsalen0.090.671218 Billard et al., 1995;Pibouin et al., 1987
 Alprazolam0.320.782-c 0.590.76 Smith et al., 1984
 Triazolam0.100.622-c 2.94.7 Smith et al., 1987
 Zolpidem0.080.762-c 4.35.7 Durand et al., 1992
Acidic compounds
 Diclofenac0.0050.552-c 4.27.6 Willis et al., 1979; Chan et al., 1987
 Ibuprofen0.010.552-c 0.81.5 Martin et al., 1990
 Tolbutamide0.040.552-c 0.20.36 Balant, 1981; Scott and Poffenbarger, 1979
 Warfarin0.010.550.0450.081 O’Reilly, 1972
 Tenidap0.00070.560.0580.10 Gardner et al., 1995
 Tenoxicam0.0090.670.020.03 Heintz et al., 1984
 Amobarbital0.391.50.530.35 Bachmann, 1987; Sawada et al., 1985
 Hexobarbital0.531.03.63.6 Breimer et al., 1975; Sawada et al., 1985
 Methohexital0.270.702-c 1116 Breimer, 1976; Gillis et al., 1976
  • 2-a All clearance values from the literature were from i.v. dosing. In the case of dependence of clearance on genetic polymorphism of drug-metabolizing enzymes, data from poor metabolizers was excluded. Nonrenal clearance values were calculated by: Clnon-renal = Cltotal · (1 − fraction of the dose excreted unchanged in urine).

  • 2-b Chlorpromazine clearance values from i.m. dose; assumes complete absorption from i.m. route.

  • 2-c Denotes blood-to-plasma ratios that were unavailable in the scientific literature. Values were determined in duplicate after incubation of drug at 1.0 μg/mL in whole blood at ambient temperature for 45 min.