TABLE 2

Correlation (r) values between metabolite rates and P450 enzyme-specific activities at 25 μM lonafarnib concentration

P450 Enzyme-Specific Reactions
P450 Involveda
M1 Formation
M2 Formation
Caffeine N3-demethylation CYP1A2 0.13 0.07
Coumarin 7-hydroxylation CYP2A6b 0.78 0.73
S-Mephenytoin N-demethylation CYP2B6b,c 0.86 0.35
Tolbutamide methyl-hydroxylation CYP2C9 0.53 0.15
S-Mephenytoin 4′-hydroxylation CYP2C19 0.25 0.06
Dextromethorphan O-demethylation CYP2D6 0.24 0.38
Chlorzoxazone 6-hydroxylation CYP2E1 0.49 0.38
Dextromethorphan N-demethylation CYP3A4 0.86d 0.40
Testosterone 6β-hydroxylation CYP3A4/5 0.93e 0.57
Lauric acid 12-hydroxylation
CYP4A11
0.11
0.02

  • ↵ a Enzyme activities are from HepatoScreen Test kit (n = 10).

  • ↵ b No metabolism was observed with CYP2A6 or CYP2B6 Supersomes.

  • ↵ c Correlation between CYP2B6 and CYP3A4 activity is high (r = 0.98); a similar observation was reported by Heyn et al. (1996).

  • ↵ d Significant; P = 0.001.

  • ↵ e Significant; P < 0.0001.