UGT inhibition risk

Evaluate the clinical risk for reversible inhibition of UGT enzymes according to the ICH M12 guideline.

Usage

basic_ugt_inhibition_risk(perp, ugt_inh)

Arguments

perp

The precipitant object.

ugt_inh

UGT inhibition data object.

Value

DDI risk object.

Details

This function assumes that the UGT inhibition data is provided as \(IC_{50}\). According to Cheng, Prusoff 1973), \(K_i\) can be assumed to be \(IC_{50}/2\) at the experimental conditions commonly used in the in vitro inhibition studies where substrate concentrations are close to \(K_M\).

The relevant metric for basic modeling of the UGT inhibition risk is \(R=C_{max,ss,u}/K_{i,u}\)

Refer to Section 2.1.2.1 of the ICH M12 guidance document) for details.

\(R>0.02\) are considered to indicate a potential UGT inhibition risk.

Examples

basic_ugt_inhibition_risk(examplinib, examplinib_ugt_inhibition)
#> ──────── Clinical DDI risk assessment ──────── 
#> UGT inhibition risk for examplinib 
#> 
#> object    ki    kiu   source      r        risk    
#> UGT1A1    15    15    study 009   0.011    FALSE   
#> UGT1A3    15    15    study 009   0.011    FALSE   
#> UGT1A4    15    15    study 009   0.011    FALSE   
#> UGT1A6    15    15    study 009   0.011    FALSE   
#> UGT1A9    3.8   3.8   study 009   0.0434   TRUE    
#> UGT2B7    15    15    study 009   0.011    FALSE   
#> UGT2B15   15    15    study 009   0.011    FALSE   
#> UGT2B17   6.1   6.1   study 009   0.027    TRUE