Drug | Fraction Unbound in Plasma (fu) | Blood-to-Plasma Ratio | Nonrenal Clearance2-a | References | |
---|---|---|---|---|---|
Plasma | Blood | ||||
ml/min/kg | |||||
Basic compounds | |||||
Chlorpromazine | 0.05 | 0.78 | 8.62-b | 11 | Dahl and Strandjard, 1974; Maxwell et al., 1972; Lund, 1980 |
Propafenone | 0.04 | 0.70 | 13 | 19 | Bryson et al., 1993 |
Verapamil | 0.10 | 0.772-c | 15 | 19 | Eichelbaum et al., 1984 |
Diphenhydramine | 0.22 | 0.652-c | 6.2 | 9.5 | Blyden et al., 1986 |
Lorcainide | 0.15 | 0.77 | 14 | 18 | Somani et al., 1987; Klotz et al., 1978 |
Diltiazem | 0.22 | 1.0 | 12 | 12 | Echizen and Eichelbaum, 1986; Smith et al., 1983 |
Amitriptyline | 0.05 | 0.86 | 10 | 12 | Schulz et al., 1983 |
Desipramine | 0.18 | 0.96 | 12 | 12 | Brosen and Gram, 1988 |
Imipramine | 0.10 | 1.1 | 13 | 12 | Sallee and Pollack, 1990; Abernathy et al., 1985 |
Ketamine | 0.88 | 0.822-c | 16 | 20 | White et al., 1985 |
Quinidine | 0.13 | 0.92 | 2.5 | 2.7 | Greenblatt et al., 1977; Rakhit et al., 1984; Hughes et al., 1975 |
Clozapine | 0.05 | 0.87 | 2.5 | 2.9 | Cheng et al., 1988 |
Neutral compounds | |||||
Dexamethasone | 0.32 | 0.93 | 3.5 | 3.8 | Tseui et al., 1979; Peterson et al., 1983 |
Prednisone | 0.25 | 0.832-c | 4.1 | 4.9 | Schalm et al., 1977 |
Diazepam | 0.013 | 0.71 | 0.4 | 0.6 | Greenblatt et al., 1980; Maguire et al., 1980 |
Midazolam | 0.05 | 0.53 | 4.6 | 8.7 | Heizmann et al., 1983 |
Methoxsalen | 0.09 | 0.67 | 12 | 18 | Billard et al., 1995;Pibouin et al., 1987 |
Alprazolam | 0.32 | 0.782-c | 0.59 | 0.76 | Smith et al., 1984 |
Triazolam | 0.10 | 0.622-c | 2.9 | 4.7 | Smith et al., 1987 |
Zolpidem | 0.08 | 0.762-c | 4.3 | 5.7 | Durand et al., 1992 |
Acidic compounds | |||||
Diclofenac | 0.005 | 0.552-c | 4.2 | 7.6 | Willis et al., 1979; Chan et al., 1987 |
Ibuprofen | 0.01 | 0.552-c | 0.8 | 1.5 | Martin et al., 1990 |
Tolbutamide | 0.04 | 0.552-c | 0.2 | 0.36 | Balant, 1981; Scott and Poffenbarger, 1979 |
Warfarin | 0.01 | 0.55 | 0.045 | 0.081 | O’Reilly, 1972 |
Tenidap | 0.0007 | 0.56 | 0.058 | 0.10 | Gardner et al., 1995 |
Tenoxicam | 0.009 | 0.67 | 0.02 | 0.03 | Heintz et al., 1984 |
Amobarbital | 0.39 | 1.5 | 0.53 | 0.35 | Bachmann, 1987; Sawada et al., 1985 |
Hexobarbital | 0.53 | 1.0 | 3.6 | 3.6 | Breimer et al., 1975; Sawada et al., 1985 |
Methohexital | 0.27 | 0.702-c | 11 | 16 | 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.