TABLE 3

Drug-metabolizing activity of CYP3A4 and CYP3A5 variants found in cynomolgus macaques

For expression of reference proteins, the expression plasmids were prepared based on cynomolgus CYP3A4 and CYP3A5 cDNA sequences (GenBank accession numbers S53047 and DQ074795, respectively) with the N-terminal modifications. For protein variants, nucleotide changes were introduced into these plasmids. Expression of protein and measurement of drug-metabolizing activities were carried out using midazolam (100 μM) and nifedipine (100 μM) as described under Materials and Methods. Results are presented as means of duplicate determinations (the ranges were less than 15% of the values).