Effect of a New Prokinetic Agent DA-9701 Formulated with Corydalis Tuber and Pharbitidis Semen on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

Table 1

Effects of DA-9701, Corydalis tuber extract (CT Ex), and Pharbitidis semen extract (PS Ex) on CYP metabolic activity in pooled human liver microsomes, H161 using cocktail substrate assay.

CYP activity	CYP	IC50, 𝜇g/mL (VDI**, L/dose)
		No preincubation			With preincubation*
		DA-9701	CT Ex	PS Ex	DA-9701	CT Ex	PS Ex
Phenacetin O-deethylation	1A2	N.I.***	N.I.	N.I.	N.I.	N.I.	N.I.
Coumarin 7-hydroxylation	2A6	N.I.	N.I.	N.I.	N.I.	N.I.	N.I.
Amodiaquine N-deethylation	2C8	N.I.	N.I.	N.I.	N.I.	N.I.	N.I.
Diclofenac 4-hydroxylation	2C9	N.I.	N.I.	N.I.	N.I.	N.I.	N.I.
S-mephenytoin 4′-hydroxylation	2C19	N.I.	145.9	N.I.	167.6 (0.18)**	130.3	N.I.
Bufuralol 1′-hydroxylation	2D6	25.9 (1.16)**	15.8	N.I.	34.3 (0.88)**	16.7	N.I.
Midazolam 1′-hydroxylation	3A4	N.I.	N.I.	N.I.	N.I.	N.I.	N.I.

*DA-9701, Corydalis tuber extract (CT Ex), and Pharbitidis semen extract (PS Ex) were preincubated for 30 min in the presence of NADPH before the addition of the substrate. **VDI: volume per dose index, ***N.I.: no inhibition at 200 𝜇g/mL of DA-9701. Cocktail substrate concentrations used for the assessment of IC₅₀ were as follows: 50 𝜇M phenacetin, 2.5 𝜇M coumarin, 2.5 𝜇M amodiaquine, 10 𝜇M diclofenac, 100 𝜇M (S)-mephenytoin, 5.0 𝜇M bufuralol, and 2.5 𝜇M midazolam. The data represent the average of three determinations.