TABLE 1

IC₅₀ values for inhibition of CYP2C8-catalyzed amodiaquine N-deethylation by various glucuronide conjugates after incubation with NADPH-fortified HLM for 0 and 30 min

Structure	Substance	Average IC₅₀^{^a}		Ratio: IC₅₀₍₀₎/IC₅₀₍₃₀₎
Structure	Substance	IC₅₀₍₀₎	IC₅₀₍₃₀₎	Ratio: IC₅₀₍₀₎/IC₅₀₍₃₀₎
		μM
	Gemfibrozil	120 ± 10	110 ± 10	1.1
	Gemfibrozil acyl-β-d-glucuronide	21 ± 1.3	1.4 ± 0.03	16
	Simvastatin acyl-β-d-glucuronide	3.8 ± 0.5	3.5 ± 0.4	1.1
	Mefenamic acyl-β-d-glucuronide	8.5 ± 0.9	8.4 ± 0.8	1.0
	Diclofenac acyl-β-d-glucuronide	14 ± 0.7	9.6 ± 0.5	1.4
	rac-Ketoprofen acyl-β-d-glucuronide	26 ± 0.7	22 ± 0.9	1.1
	Indomethacin acyl-β-d-glucuronide	26 ± 2.2	26 ± 2.3	1.0
	Atorvastatin acyl-β-d-glucuronide	45 ± 3.7	35 ± 3.1	1.3
	Ibuprofen acyl-β-d-glucuronide	>100 (39 ± 4)^{^b}	>100 (47 ± 4)^{^b}	>1.0
	(R)-Naproxen acyl-β-d-glucuronide	>100 (27 ± 6)^{^b}	>100 (37 ± 4)^{^b}	<1.0
	(S)-Naproxen acyl-β-d-glucuronide	>100 (17 ± 6)^{^b}	>100 (16 ± 7)^{^b}	1.0
	Dihydro-ketoprofen acyl-β-d-glucuronide	>100 (1 ± 5)^{^b}	>100 (5 ± 6)^{^b}	1.0

↵a Data are reported as the mean ± S.D. of n = 4 determinations. IC₅₀₍₀₎ and IC₅₀₍₃₀₎ represent the IC₅₀ determined after 0 and 30 min of incubation with NADPH-fortified HLM.
↵b %inhibition observed at 100 μM ± S.D.