Comparison of intrinsic metabolic clearance in fresh and cryopreserved human hepatocytes.

1. We compared the intrinsic clearance (CL_int) of a number of substrates in suspensions of fresh and cryopreserved human hepatocytes from seven donors. 2. CL_int values for a cocktail incubation of phenacetin, diclofenac, diazepam, bufuralol, midazolam, and hydroxycoumarin were 4.9 ± 3.4, 18 ± 7.2, 5.1 ± 4.9, 6.3 ± 3.3, 9.8 ± 5.8 and 22 ± 14 μl min^-1/106 cells, respectively, and they correlated well with corresponding CL_int values using cryopreserved hepatocytes from 25 different donors. 3. CL_int values of each cocktail substrate and 20 AstraZeneca new chemical entities were compared in fresh and cryopreserved hepatocytes from the same three donors. There was a statistically significant correlation between CL_int in fresh and cryopreserved hepatocytes for each of the three livers (p < 0.002) and the geometric mean of the ratio of fresh to cryopreserved CL_int values was 1.03. 4. In conclusion, the results add further support to the use of cryopreserved human hepatocytes as a screening model for the intrinsic clearance of new chemical entities. [ABSTRACT FROM AUTHOR]