PK CIA
Assessment of CYP inhibition potential and DDI risk for a test compound by quantifying reversible and time-dependent (mechanism-based) inhibition across major CYP isoforms; reporting AUCR metrics and inhibition strength categories.
Needs steward attention
Assay metadata
Rendered from the governed metadata model.
- Assay type hierarchy
- bioassay
- ›pharmacokinetic assay
- ›drug–drug interaction assay
- ›CYP inhibition assay
- ›cocktail inhibition assay
- Assay type *
- cocktail inhibition assay
- Experimental setting *
- in vitro
- Assay format *
- cell-based
- Assay design
- 7-plex CYP cocktail
- Target *
- CYP1A1CYP1A2CYP2C8CYP2C9CYP2C19CYP2D6CYP3A4
- Biological process
- drug metabolism
- Molecule role *
- test item
- Cell system
- human hepatocytes
- Species
- Not set
- Donor source
- Not set
- Plating format
- Not set
- Incubation duration
- Not set
- Detection type *
- UPLC-MS/MS
- Physical detection method *
- mass spectrometry
- Reference gene
- Not set
- Expected readout *
- AUCR
Description
Cocktail Inhibition Assay (CIA): The potential of test compounds to inhibit human cytochrome P450 isoforms (mainly CYP1A2, 2C8, 2C9, 2D6 and 3A4) is investigated with human hepatocytes in suspension. Test compounds (usually 5 µM) are mixed with a cocktail of CYP isoform-specific substrates (mainly phenacetin, repaglinide, diclofenac, dextromethorphan and midazolam) and incubated with hepatocytes in suspension for up to 1.5 h (co-incubation) or up to 3.5 h (pre-incubation) at 37°C to obtain clearance values. Clearance values are obtained by measurement of the substrate depletion via LC/MS analysis. As a control serves the incubation of substrate cocktail in the absence of the test compound. Inhibitory effects are determined by comparison of the clearance values for the isoform-specific substrates in the presence and absence of a potential inhibitor in co- and pre-incubation (the latter for evaluation of time-dependent inhibition). Finally, clearance ratios are calculated. A cocktail of standard inhibitors, specifically inhibiting a single CYP isoform, is always included.
Review history
This template has not been reviewed yet.
Change history
Started v2 as a draft copy of v1
Dr Amelia Ostrowski · 20/08/2026, 05:15:49
Imported from PK CIA.json
Dr Amelia Ostrowski · 18/08/2026, 19:33:36