TABLE 4

Maximal fold induction of cytochrome P450 mRNA and activity by statin treatment of human hepatocytes

Values represent the maximal fold induction observed with the time point given in parentheses.

P450PhenotypePhenobarbitalRifampicinAtorvastatinLovastatinPravastatinRosuvastatinSimvastatin
CYP1A2mRNA2.3 (72 h)2.2 (48 h)3.2 (24 h)1.9 (24 h)2.3 (72 h)2.4 (24 h)2.4 (48 h)
Activity2.4 (96 h)2.1 (72 h)2.2 (48 h)1.9 (48 h)1.6 (48 h)2.0 (48 h)2.1 (48 h)
CYP2B6mRNA24.1 (72 h)9.8 (48 h)18.7 (72 h)3.8 (72 h)4.4 (72 h)1.2 (24 h)19.3 (72 h)
Activity10.5 (72 h)11.1 (96 h)11.1 (72 h)3.0 (48 h)0.9 (96 h)0.7 (48 h)4.2 (72 h)
CYP2C8mRNA104.3 (48 h)11.6 (48 h)11.6 (72 h)3.1 (24 h)5.1 (48 h)4.2 (48 h)17.1 (48 h)
Activity7.1 (72 h)8.3 (72 h)19.7 (72 h)9.9 (72 h)1.6 (48 h)6.0 (72 h)10.6 (72 h)
CYP2C9mRNA14.6 (72 h)5.6 (48 h)10.5 (48 h)2.7 (96 h)8.3 (96 h)3.9 (48 h)7.0 (72 h)
Activity6.5 (96 h)6.2 (96 h)8.8 (72 h)3.1 (96 h)1.6 (96 h)2.1 (72 h)4.1 (72 h)
CYP2C19mRNA4.8 (72 h)3.0 (48 h)2.7 (24 h)2.4 (24 h)5.3 (72 h)2.6 (48 h)2.3 (72 h)
Activity1.5 (48 h)2.8 (48 h)1.8 (48 h)1.8 (48 h)1.0 (48,96)1.6 (72 h)2.4 (72 h)
CYP2D6mRNA3.2 (72 h)1.5 (48 h)2.7 (72 h)1.6 (96 h)2.3 (96 h)3.7 (48 h)5.7 (72 h)
Activity1.1 (48–72 h)1.2 (24–48 h)3.6 (96 h)15 (72–96 h)1.2 (48–96 h)2.8 (96 h)1.7 (72–96 h)
CYP3A4mRNA116.2 (72 h)33.5 (48 h)127.4 (72 h)16.8 (72 h)3.0 (72 h)17.3 (48 h)107.3 (72 h)
Activity6.8 (72 h)5.0 (72 h)10.8 (72 h)5.2 (96 h)1.2 (48 h)3.8 (48 h)5.7 (48 h)