TABLE 1

Cytochrome P450 (P450)-selective inhibitors and recommended concentration range to use in vitro phenotyping studies

P450 EnzymeProbe Substrate (median reported Km value)aSelective InhibitorInhibitor Median Reported Ki or IC50 valueaRecommended Experimental Inhibitor Concentration Range
µMµMµM
CYP1A2Phenacetin (28)Furafyllineb1.90.01–10
CYP2A6Coumarin (2.5)Methoxsalenc0.480.005–5
Tranylcypromine0.300.005–5
CYP2B6Bupropion (68)Ticlopidineb,d0.170.005–5
PPPe5.50.025–25
thio-TEPAf5.70.025–25
CYP2C8Amodiaquine (3)Montelukastg0.0190.002–2
CYP2C9Tolbutamide (125)Sulfaphenazole0.500.005–5
Diclofenac (5)
CYP2C19S-mephenytoin (40)Ticlopidineb,d1.20.01–10
(+)-N-3-benzyl-nirvanol0.240.005–5
CYP2D6Bufuralol (9)Quinidine0.0580.002–2
CYP2E1Chlorzoxazone (74)Diethythiocarbamate5.30.025–25
CYP3A4/5Midazolam (3.5)Ketoconazole0.100.001–1
Testosterone (54)Azamulinb0.150.005–5
Nifedipine (12)
  • a The University of Washington Metabolism and Transport Drug Interaction Database (http://www.druginteractioninfo.org) was queried in the category of “In vitro Parameters” for studies providing Km values for the indicated substrates or Ki or IC50 values for the indicated precipitants. If more than one P450 was inhibited by the selected precipitant for a particular substrate metabolism, the corresponding Ki or IC50 values were excluded from the analysis. If individual Ki or IC50 values were listed for one study, the average was taken. If a range of values were given, the lowest value was taken. All queries were of data reported in the Database as of Jan 2013 or Nov 2015.

  • b Time-dependent inhibitor, preincubation recommended (e.g., 15 min at 37°C before substrate addition).

  • c Methoxsalen also inhibits CYP1A2 (median IC50 or Ki value of 0.70 μM).

  • d Ticlopidine inhibits both CYP2B6 and CYP2C19.

  • e 2-phenyl-2-(1-piperdinyl)propane.

  • f N,N,N-triethylene thiophosphoramide.

  • g IC50 dependent upon microsomal protein concentration due to substantial microsomal protein binding of montelukast (Walsky et al., 2005).