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Drug transporter inhibition risk

transporter_inhibition_risk.Rd

Drug transporter inhibition risk

Usage

transporter_inhibition_risk(
  perp,
  transporter_inh,
  transporter_ref = transporter_reference_data
)

Arguments

perp

The perpetrator object.

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.

transporter_ref

Transporter reference data, see transporter_reference_data for details.

Value

A data frame.

Details

The metric for the assessment of transporter interactions is \(R=[I]/IC_{50}\).

The relevant perpetrator concentrations \([I]\) and regulatory thresholds of concern are:

Itransporterthreshold
\(I_{gut}\)P-gp and BRCR when drugs are orally administered10
\(C_{max,ss,u}\)P-gp and BRCR when drugs are administered parenterally or for drug metabolites0.02
\(I_{max,inlet,u}\)hepatic basolateral transporters OCT1, OATP1B1 and OATP1B30.1
\(C_{max,ss,u}\)renal basolateral transporters OAT1, OAT3 and OCT20.1
\(C_{max,ss,u}\)apical transporters MATE1 and MATE2-K0.02

See also

transporter_inhibition_risk_table()

read_transporter_inhibitor_data()

Examples

transporter_inhibition_risk(examplinib_parent,
  examplinib_transporter_inhibition_data)
#>    transporter   ic50    source          i            r threshold  risk
#> 1      Pgp_int   0.41 study 005       igut 8.912391e+03     10.00  TRUE
#> 2      Pgp_sys   0.41 study 005    imaxssu 4.019984e-01      0.02  TRUE
#> 3     BCRP_int   1.90 study 005       igut 1.923200e+03     10.00  TRUE
#> 4     BCRP_sys   1.90 study 005    imaxssu 8.674701e-02      0.02  TRUE
#> 5      OATP1B1 177.00 study 006 imaxinletu 1.090047e-03      0.10 FALSE
#> 6      OATP1B3  35.00 study 006 imaxinletu 5.512525e-03      0.10 FALSE
#> 7         OAT1 271.00              imaxssu 6.081894e-04      0.10 FALSE
#> 8         OAT3 300.00              imaxssu 5.493978e-04      0.10 FALSE
#> 9         BSEP  12.80              imaxssu 1.287651e-02      0.10 FALSE
#> 10        OCT1   2.30 study 006       <NA>           NA        NA    NA
#> 11        OCT2  67.00 study 006    imaxssu 2.459990e-03      0.10 FALSE
#> 12       MATE1   3.60 study 006    imaxssu 4.578315e-02      0.02  TRUE
#> 13      MATE2k   1.10 study 006    imaxssu 1.498358e-01      0.02  TRUE