TABLE 4

Comparison of IC₅₀ values estimated using the individual substrate and the substrate cocktails of well known P450- and UGT-selective inhibitors

Inhibitors of P450 and UGT enzymes were incubated with each substrate cocktail set and with individual substrate alone. IC₅₀ values were calculated using a nonlinear least-squares regression analysis.

Enzyme	Substrates	Inhibitors	IC₅₀ (μM ± S.D.)^{^a}			References
Enzyme	Substrates	Inhibitors	Individual Substrate	Cocktail Substrate	Literature	References
CYP1A2	Phenacetin	α-Naphthoflavone	0.014 ± 0.003	0.013 ± 0.004	0.01–0.27	(Gao et al., 2007; Zhang et al., 2008; Perloff et al., 2009)
CYP2C9	Diclofenac	Sulfaphenazole	0.70 ± 0.08	0.68 ± 0.08	0.3–1.5	(Dierks et al., 2001; Kim et al., 2005)
CYP2C19	S-mephenytoin	S-benzylnirvanol	1.02 ± 0.13	1.20 ± 0.06	0.4–0.41	(Walsky and Obach, 2003; Walsky and Obach, 2004)
CYP2D6	Dextromethorphan	Quinidine	0.11 ± 0.01	0.13 ± 0.01	0.02–0.68	(Dierks et al., 2001; Kim et al., 2005)
CYP3A	Midazolam	Ketoconazole	0.038 ± 0.001	0.032 ± 0.0004	0.09–0.24	(Dierks et al., 2001; Kim et al., 2005)
UGT1A1	SN-38	Atazanavir	0.37 ± 0.11	0.38 ± 0.13	0.4–2.5	(Zhang et al., 2005)
UGT1A4	Trifluoperazine	Hecogenin	0.89 ± 0.21	0.86 ± 0.11	0.64–1.5	(Uchaipichat et al., 2006)
UGT1A9	Mycophenolic acid	Niflumic acid	0.78 ± 0.10	0.83 ± 0.18	0.1–8	(Vietri et al., 2000; Mano et al., 2006; Miners et al., 2011)
UGT2B7	Naloxone	Mefenamic acid	4.18 ± 1.01	5.04 ± 1.34	0.3–370	(Mano et al., 2007; Knights et al., 2009)

↵^a Values represent the mean (±S.D.) of experiments performed in triplicate.