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Overall DDI risk summary text block

ddi_risk_summary.Rd

[Experimental]

Usage

ddi_risk_summary(
  perp,
  cyp_inh = NULL,
  cyp_tdi = NULL,
  cyp_ind = NULL,
  ugt_inh = NULL,
  transporter_inh = NULL,
  d = 1,
  include_induction = TRUE,
  substr = cyp_reference_substrates,
  cyp_kdeg = cyp_turnover
)

Arguments

perp

The perpetrator object.

cyp_inh

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

  • 'name' The name of the perpetrator compound.

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

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

  • 'source' Optional source information as character.

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_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.

ugt_inh

UGT inhibition data as data frame, The following fields are expected:

  • 'name' The name of the perpetrator compound.

  • 'ugt' The UGT enzyme as (upper case) character.

  • 'ic50' The \(IC_{50}\) in \(\mu M\) as numeric.

  • 'source' Optional source information as character.

transporter_inh

Transporter inhibition data as data frame. The following fields are expected:

  • 'name' The perpetrator compound name.

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

  • 'ic50' The \(IC_{50}\) of the inhibition in μM.

  • 'source' Optional source information as character.

d

Scaling factor, defaults to 1.

include_induction

Switch to define whether induction effects should be included in the calculation (C-terms as per the FDA guideline)

substr

The CYP probe substrates to be used as data frame, defaults to cyp_reference_substrates. The data frame is expected to have the following fields:

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

  • 'substrate' The substrate name as character.

  • 'fgut' The fraction of the drug escaping gut metabolism.

  • 'fm' The fraction of the drug that undergoes hepatic metabolism.

  • 'fmcyp' The fraction metabolized by the respective CYP enzyme.

cyp_kdeg

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

Value

Markdown-formatted text output.

Examples

ddi_risk_summary(examplinib_compounds, examplinib_cyp_inhibition_data,
  examplinib_cyp_tdi_data, examplinib_cyp_induction_data,
  examplinib_ugt_inhibition_data, examplinib_transporter_inhibition_data)
#> [1] "* examplinib has a clinical risk for direct inhibition of CYP2C9 and CYP2C19 (basic modeling)\n* examplinib has a clinical risk for time-dependent inhibition of CYP3A4\n* examplinib has a clinical risk for induction of CYP3A4 (fold-change method)\n* examplinib has a clinical risk for induction of CYP3A4 (basic kinetic method)\n* M1 has a clinical risk for induction of CYP2B6 and CYP3A4 (fold-change method)\n* M1 has a clinical risk for induction of CYP2B6 and CYP3A4 (basic kinetic method)\n* based on mechanistic-static modeling (S-warfarin and omeprazole), examplinib has a clinical risk for inhibition of CYP2C9 and CYP2C19\n* based on mechanistic-static modeling (midazolam), examplinib has a clinical risk for induction of CYP3A4\n* examplinib has a clinical risk for inhibition of UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7, UGT2B15 and UGT2B17\n* M1 has a clinical risk for inhibition of UGT1A1 and UGT2B17\n* examplinib has a clinical risk for inhibition of P-gp (intestinal), P-gp (hepatic), BCRP (intestinal), BCRP (hepatic), MATE1 and MATE2k"
ddi_risk_summary(examplinib_parent, examplinib_cyp_inhibition_data)
#> [1] "* examplinib has a clinical risk for direct inhibition of CYP2C9 and CYP2C19 (basic modeling)\n* based on mechanistic-static modeling (S-warfarin and omeprazole), examplinib has a clinical risk for inhibition of CYP2C9 and CYP2C19"