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Basic static CYP induction risk

static_cyp_induction_risk.Rd

Basic static CYP induction risk

Usage

static_cyp_induction_risk(perp, cyp_ind)

Arguments

perp

The perpetrator object or a list thereof.

cyp_ind

The CYP induction data as data frame. The following fields are expected:

  • 'name' The name of the perpetrator compound as character.

  • 'cyp' The CYP enzyme as (upper case) character.

  • 'emax' The \(E_{max}\), i.e., the maximum induction effect determined in vitro as numeric.

  • 'ec50' The \(EC_{50}\) in \(\mu M\) as numeric.

  • 'maxc' The maximal concentration in \(\mu M\) tested in the in vitro assay as numeric.

  • 'source' Optional source information as character.

Value

A data frame.

Details

The basic fold-change method evaluates whether the maximal fold-change in mRNA expression for the CYP enzyme, relative to the vehicle control, is > 2-fold at concentrations up to 50-fold over the unbound Cmax,ss - provided that concentration-dependent increases in mRNA were observed in vitro.

If in the in vitro experiments concentrations of 50-fold the unbound Cmax,ss were not tested, this is noted in the output.

Also note that the ICH guideline further specifies that the positive control used in the in vitro studies should result in at least 6-fold mRNA increases, otherwise an induction risk cannot be ruled out if the mRNA increase for the CYP enzyme is > 20% of the positive control. This, as well as the condition of concentration-dependent increase in mRNA increase (see above), must be confirmed manually by the user.

For details, refer to section 2.1.4.1 of the ICH M1s2 guideline

Examples

static_cyp_induction_risk(examplinib_parent, examplinib_cyp_induction_data)
#>       cyp emax maxc    source maxc_imaxssu  risk
#> 1  CYP1A2 1.00    5 study 007         30.3 FALSE
#> 2  CYP2B6 1.00    5 study 007         30.3 FALSE
#> 3  CYP2C8   NA   NA                     NA    NA
#> 4  CYP2C9   NA   NA                     NA    NA
#> 5 CYP2C19   NA   NA                     NA    NA
#> 6  CYP2D6   NA   NA                     NA    NA
#> 7  CYP3A4 7.35    3 study 007         18.2  TRUE
#>                                                                 note
#> 1 caution: maximal tested concentration is less than 50-fold Cmax,u!
#> 2 caution: maximal tested concentration is less than 50-fold Cmax,u!
#> 3                                                                   
#> 4                                                                   
#> 5                                                                   
#> 6                                                                   
#> 7 caution: maximal tested concentration is less than 50-fold Cmax,u!