TABLE 6

Inhibition of human UDP-glucuronosyltransferase activities in human liver microsomes and recombinant UGT enzymes

Inhibitor and Incubation Conditions^{^a}	IC₅₀^{^b}
Inhibitor and Incubation Conditions^{^a}	UGT1A1	UGT1A4	UGT1A6	UGT1A9	UGT2B7
	μM
Chrysin
HLM	4.6	38	>100^{^c,^d}	43	15
HLM + BSA	24	>100	>100^{^c}	26	>100^{^c}
rUGT	6.1	43	22	>100^{^c}	23
rUGT + BSA	13	>100^{^c}	>100^{^c}	>100^{^c}	>100^{^c}
Itraconazole
HLM	0.42	0.97	>100^{^c}	>100^{^c}	>100^{^c}
HLM + BSA	1.5	0.71	>100^{^c}	>100^{^c}	>100^{^c}
rUGT	36	0.70	>100^{^c}	>100^{^c}	>100^{^c}
rUGT + BSA	>100^{^c}	1.06	>100^{^c}	>100^{^c}	>100^{^c}

↵a HLMs or rUGT (0.025 mg/ml) were fully activated with alamethicin (10 μg/ml) and incubated with increasing inhibitor concentrations (0.1–100 μM) in 100 mM Tris-HCl (pH = 7.5) buffer containing 5 mM MgCl₂, 5 mM UDPGA, with or without 2% BSA, as described under Materials and Methods. UGT substrate concentrations were at or below K_m; ES (10 μM or 100 μM with BSA), TFP (40 μM HLM or 67 μM with BSA; 10 μM rUGT or 140 μM with BSA), 5HTOL (350 μM), PRO (100 μM HLM, 200 μM rUGT, or 40 μM with BSA), AZT (842 μM HLM, 1080 μM rUGT, 374 μM HLM with BSA, or 596 μM rUGT with BSA).
↵b IC₅₀ values represent mean from two experiments and are not corrected for nonspecific binding.
↵c Negligible or low degree of inhibition (IC₅₀ > 100 μM).
↵d Low degree of inhibition, 40% activity remaining at 100 μM chrysin.