CYP Inhibition

The inhibition of CYP isoenzymes is one of the key aspects in drug-drug interaction.

Determination of the IC₅₀

The IC₅₀ of the test item for a specific CYP marker reaction or drug-drug interaction is determined.

Quantity of test item required: 15 mg
Turnaround time of draft report: 15 working days

Study Design

• one CYP isoform (microsomes or human recombinant enzymes)
• triplicates
• one concentration of CYP
• one concentration of marker substrate
• seven to ten concentrations of test item
• one time point
• negative controls: CYP marker reactions:

1A1/2 (7-ethoxyresorufin O-deethylation)
2A6 (coumarin 7-hydroxylation)
2B6 (S-mephenytoin N-demethylation)
2C8 (paclitaxel 6a-hydroxylation)
2C9 (diclofenac 4'-hydroxylation)
2C19 (S-mephenytoin 4'-hydroxylation)
2D6 (bufuralol-hydroxylation)
2E1 (chloroxazone 6-hydroxylation)
3A4/5 (testosterone 6ß-hydroxylation)
4A11 (lauric acid-hydroxylation)
11B1 (11-deoxycortisol 11ß-hydroxylation)
11B2 (deoxycorticosterone-hydroxylation)

• negative controls: CYP marker reactions:

1A1/2 (furafylline)
2A6 (8-methoxypsoralene)
2B6 (triethylenethiophosphoramide)
2C8 (ketoconazole)
2C9 (sulfaphenazole)
2C19 (omeprazole)
2D6 (quinidine)
2E1 (diethyldithiocarbamate)
3A4/5 (ketoconazole)
4A11 (10-(imidazolyl)-decanoic scid)
11B1 (metyrapone)
11B2 (ketoconazole)

Analytics

• detection of metabolite formed in the marker reaction