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Basic modeling of the CYP time-dependent inhibition risk

basic_cyp_tdi_risk.Rd

This function calculates the risk for time-dependent inhibition of CYP enzymes.

Usage

basic_cyp_tdi_risk(perp, cyp_tdi, cyp_kdeg = cyp_turnover)

Arguments

perp

The perpetrator object.

cyp_tdi

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

  • 'name' The perpetrator compound name as character.

  • 'cyp' The CYP enzyme as character.

  • 'ki' The \(K_I\) in \(\mu M\) as numeric.

  • 'kinact' The \(k_{inact}\) in 1/h as numeric.

  • 'source' Optional source information as character,

cyp_kdeg

The CYP turnover data as data frame. Defaults to the built-in reference data, cyp_turnover.

Value

A data frame.

Details

The risk assessment is based on:

$$R=\frac {k_{obs} + k_{deg}}{k_{deg}}$$

where

$$k_{obs}=\frac {5*k_{inact}*C_{max,u}}{K_{I,u} + 5 * C_{max,u}}$$

Values of \(R > 1.25\) suggest a relevant TDI potential.

The CYP degradation rates, \(k_{deg}\) are physiological constants that should be derived from the scientific literature. This package provides standard values for \(k_{deg}\) in cyp_turnover that are commonly used.

In the present version, only the risk for hepatic TDI for CYP enzymes is calculated.

See also

cyp_turnover

read_tdi_data()

Examples

basic_cyp_tdi_risk(examplinib_parent, examplinib_cyp_tdi_data)
#>      cyp   ki    fu kinact   kdeg    source        r risk
#> 1 CYP3A4 0.17 0.023   0.04 0.0193 study 001 2.718115 TRUE