TABLE 2.
Drug-specific parameters
| Compound | Class | fup (n = 4)a | fum (n = 4)a | Log P | pKa,a | pKa,b | BP | Log Dvo | CL | Reference |
|---|---|---|---|---|---|---|---|---|---|---|
| l/h | ||||||||||
| Betaxolol | B | 0.50 (12%) | 0.77 (3%) | 2.81 | 14 | 9.4 | 2b | 1.78 | 10.2 | Riddell et al., 1987; Recanatini, 1992; Rodgers and Rowland, 2007 |
| Diltiazem | B | 0.26 (8%) | 0.48 (2%) | 2.7 | 14 | 7.7 | 1 | 1.88 | 97.5 | Rekker and Mannhold, 1992; Obach, 1999; Ishihama et al., 2002 |
| Diphenhydramine | B | 0.44 (4%) | 0.84 (4%) | 3.27 | 14 | 8.98 | 0.74 | 2.30 | 43 | Albert et al., 1975; Sangster, 1994; Hansch et al., 1995; Obach, 1999 |
| Metoprolol | B | 0.87 (17%) | 0.80 (3%) | 1.88 | 14 | 9.7 | 1.14 | 0.746 | 58.8 | Hansch et al., 1995; Rodgers and Rowland, 2007 |
| Mibefradil | B | 0.031 (11%) | 0.034 (15%) | 3.07 | 14 | 10.2 | 0.64 | 2.07 | 15.5 | Welker et al., 1998; Nagar and Korzekwa, 2017 |
| Nicardipine | B | 0.0024 (7%) | 0.039 (12%) | 3.82 | 14 | 8.6 | 0.71 | 2.90 | 31.2 | Sangster, 1993; Rodgers and Rowland, 2007 |
| Quinidine | B | 0.15 (8%) | 0.815 (10%) | 3.52 | 14 | 8.94 | 0.92 | 2.07 | 14 | Sangster, 1994; Obach, 1999; Nagar and Korzekwa, 2017 |
| Verapamil | B | 0.088 (20%) | 0.37 (19%) | 3.79 | 14 | 8.92 | 0.74 | 2.88 | 49 | Sangster, 1994; Hansch et al., 1995; Robinson and Mehvar, 1996; Obach, 1999 |
| Caffeine | N | 0.72c | 0.98 (6%) | −0.07 | 14 | 1.04 | 1.01 | −1.43 | 5.2 | Hansch et al., 1995; Rodgers and Rowland, 2007 |
| Diazepam | N | 0.012 (9%) | 0.74 (4%) | 2.82 | 14 | 3.4 | 0.64 | 1.79 | 1.33 | Maguire et al., 1980; Sangster, 1993; O’Neil, 2006 |
| Felodipine | N | 0.0017 (12%) | 0.023 (27%) | 3.86 | 14 | 5.07 | 0.7 | 2.95 | 41.7 | Diez et al., 1991; Uchimura et al., 2010; Pandey et al., 2013 |
| Fluconazole | N | 0.93 (14%) | 0.94 (14%) | 0.8 | 14 | 1.77 | 1 | −0.79 | 1.25 | Debruyne et al., 1987; Debruyne, 1997; Rodgers and Rowland, 2007 |
| Midazolam | N | 0.033 (4%) | 0.71 (4%) | 3.15 | 14 | 6.01 | 0.53 | 2.16 | 18 | Heizmann et al., 1983; Rodgers and Rowland, 2007 |
| Phenytoin | N | 0.18 (7%) | 0.83 (3%) | 2.21 | 8.32 | 1 | 0.61 | 1.11 | 1.61 | Stella et al., 1998; Brittain, 2007; Uchimura et al., 2010 |
| Diclofenac | A | 0.0014 (18%) | 0.78 (4%) | 4.51 | 4.15 | 1 | 0.55 | 3.68 | 17.6 | Sangster, 1994; Obach, 1999; Avdeef, 2003 |
| Glyburide | A | 0.0012 (16%) | 0.72 (9%) | 4.29 | 5.38 | 1 | 0.57 | 2.59 | 4.81 | Austin et al., 2002; Li et al., 2017 |
| Ketoprofen | A | 0.0041 (9%) | 0.95 (4%) | 3.12 | 4.45 | 1 | 0.56 | 2.06 | 5.02 | Sangster, 1993, 1994; Rodgers and Rowland, 2007; Ye et al., 2016 |
| Nafcillin | A | 0.123 (6%) | 0.94 (14%) | 2.7 | 2.6 | 1 | 0.55d | 1.66 | 33.9 | Wishart et al., 2018 |
| Warfarin | A | 0.0076 (13%) | 0.98 (16%) | 2.7 | 5.05 | 1 | 0.55 | 1.66 | 0.179 | Hiskey et al., 1962; Hansch et al., 1995; Obach, 1999 |
A, acids; B, bases; N, neutral; CL, clearance; vo, vegetable oil.
a
All 98 experimental values unless otherwise noted.
b
Rat BP was used.
c
An average of literature values was used.
d
0.55 was used (1-hematocrit).