TABLE 1

Data for human hepatocyte incubations conducted in the absence of fetal calf serum (corrected for both fub and fuinc)

Compound
Chemical Class
fub
CLint, ub, in vivo
CLh
Predicted
Observed
Predicted
Observed
ml/min/kg ml/min/kg
Diclofenaca A 0.0055 618.36 2083.46 2.92 7.33
Diflunisalb A 0.0053 9.86 34.8 0.05 0.18
Etodolacb A 0.02 81.2 82.84 1.28 1.31
Fenoprofenb A 0.01 56.52 216.15 0.47 1.69
Furosemidea A 0.029 5.95 22.85 0.14 0.59
Gemfibrozilb A 0.005 325.82 773.37 1.43 3.09
Glipizideb A 0.02 7.13 60.52 0.12 0.96
Ibuprofena A 0.0182 71.34 82.7 0.64 1.4
Indomethacinb A 0.02 27.13 145.77 0.46 2.24
Irbesartanb A 0.04 58.75 131.31 1.93 3.85
Ketoprofenb A 0.02 22.44 103.95 0.52 2.22
Montelukastb A 0.0009 96.27 1495.15 0.09 1.27
Oxaprozinb A 0.0007 24.4 100.36 0.02 0.07
Tenoxicamc A 0.0164 8.77 4.46 0.14 0.073
Tolbutamidea A 0.04 6.91 8.99 0.24 0.3
Troglitazoned A 0.0017 306.36 10000 0.51 9
Warfarinc A 0.018 3.69 8.22 0.07 0.16
Buspironee B 0.05 613.8 1582 12.11 19.2f
Carvedilolb B 0.03 281.58 521.97 5.87 8.7
Chlorpromazinec B 0.03 230.33 502.92 5.14 8.6
Cimetidineb B 0.9 3.35 4.23 2.62 3.2
Desipraminec B 0.17 127.16 124.92 10.39 10.3
Diltiazema B 0.22 77.81 143.61 10.70 12.8
Granisetronb B 0.7 29.72 35.14 10.17 11
Imipraminea B 0.1 92.57 125.59 6.33 9.46
Lidocainee B 0.3 24.61 100.68 5.34 15.0
Metoprolola B 0.747 13.87 40.62 5.95 12.15
Naloxonea B 0.56 150.28 924.35 16.16 19.5f
Pindololb B 0.9 9.28 5.91 5.89 4.2
Propranolola B 0.12 59.2 291.87 6.46 16.11
Quinidine B 0.15 12.95 48.63 1.73 5.33
Ranitidineb B 0.77 3 4.4 2.07 2.9
Timolole B 0.4 6.55 22.75 2.32 9.17
Tiprolidine B 0.1 39.61 133.33 3.31 8
Verapamila B 0.115 278.92 388.33 11.65 14.66
Acetaminophend N 0.79 2.53 6.71 1.81 4
Antipyrinea N 0.94 0.82 0.69 0.74 0.6
Caffeinea N 0.685 2.89 2.25 2.07 1.4
Cyclosporin Ab N 0.04 13.46 155.27 0.52 4.7
Diazepama N 0.012 6.41 31.29 0.08 0.43
FK079d N 0.0288 56.38 636 0.91 4.4
FK1052d N 0.021 32.38 1570 0.64 12.2
FK480d N 0.008 49.41 336 0.40 2.4
Lorazepamc N 0.094 1.16 12.38 0.11 1.1
Methylprednisolonec N 0.23 37.08 52.17 5.98 7.5
Midazolamc N 0.04 40.08 246.27 1.48 6.6
Nifedipinea N 0.05 32.6 253.7 1.46 7.8
Ondansetronb N 0.68 5.23 12.4 3.00 5.9
Oxazepamc N 0.03 8.23 38.8 0.24 1.1
Phenacetine N 0.594 76.01 212.5 13.90 19.2f
Prazosinb N 0.07 6.16 42.23 0.45 2.7
Prednisolonec N 0.26 35.54 59.22 6.32 8.7
Ritonavirb N 0.0148 30.51 86.26 0.44 1.2
Sildenafilc N 0.04 24.35 214.29 0.93 6
Theophyllinec N 0.4 1.67 1.68 0.65 0.65
Zidovudined
N
0.8
9.87
42.1
5.66
12.4

  • A, acid; B, base; N, neutral.

  • ↵ a-e Data were obtained from a mean data (see Table 4); b this laboratory; c Lau et al. (2002); d Naritomi et al. (2003); e Shibata et al. (2004).

  • ↵ f Recalculated from data provided in original reference, assuming oral bioavailability = hepatic availability = 1 - CLh/(RB × Qh). CLint, ub, in vivo was calculated from the dispersion model using the Excel Goal Seek tool.