TABLE 3

CLint estimates determined from fresh and cryopreserved dog and human hepatocytes Results are expressed as the mean CLint ± standard deviation from five human and six dog donors. Results not expressing a S.D. are from two donors only. The CLint determinations were carried out as described under Materials and Methods. The CLint estimates reported in Table 1 represent a different donor pool from the one reported in this table, which can result in different mean values for the same substrate.


Compounds

CLint
Human hepatocytes
Dog hepatocytes
Fresh
Cryo
Fresh
Cryo
μl/min/106 cells μl/min/106 cells
Dextromethorphan 16 ± 8 15 ± 6 64 ± 13 56 ± 29
Diazepam <1 <1 >150 >150
Diclofenac 47 ± 22 44 ± 14 12 ± 5 11 ± 4
Diltiazem 13 ± 4 13 ± 3 29 ± 10 20 ± 9
Ethinylestradiol 7 ± 2 5 ± 3 69 83
Gemfibrozil 24 ± 5 20 ± 5 13 ± 1 11 ± 2
Imipramine 4 7 ± 3 32 ± 10 45 ± 26
Ketoprofen 4 ± 2 1 ± 1 4 ± 0.4 3 ± 2
Metoprolol 7 ± 6 10 ± 3 11 ± 4 13 ± 12
Midazolam 14 ± 8 11 ± 3 125 114
Naproxen 5 ± 2 3 ± 3 3 ± 1 3 ± 1
Propofol 107 ± 26 92 ± 36 >150 >150
Propranolol 15 ± 5 19 ± 3 38 ± 10 33 ± 16
Verapamil
42 ± 8
43 ± 17
38 ± 12
35 ± 17