This package provides functions for the calculation and documentation of the potential of drugs to act as perpetrators of clinically relevant drug-drug interaction (DDI).
Installation
You can install the development version of ddir like so:
devtools::install_github("rstrotmann/ddir")Example
The package provides sample data for a fictional drug, examplinib. The following code shows the relevant drug properties for examplinib, and calculates the perpetrator DDI risk for direct CYP inhibition (basic method). Both are provided as markdown-formatted output tables:
library(ddir)
p <- examplinib_parent
property_table(p)| parameter | value | source |
|---|---|---|
| oral | TRUE | |
| \(MW\) (g/mol) | 492.6 | |
| \(dose\) (mg) | 450 | clinical dose |
| \(C_{max,ss}\) (ng/ml) | 3530 | study 001 |
| \(f_u\) | 0.023 | study 002 |
| \(f_{u,mic}\) | 1 | default |
| \(R_B\) | 1 | study 003 |
| \(F_a\) | 0.81 | study 003 |
| \(F_g\) | 1 | default |
| \(k_a\) (1/min) | 0.00267 | unknown |
| \(solubility\) (mg/l) | Inf | default |
Compound parameters for examplinib
basic_cyp_inhibition_risk_table(p, examplinib_cyp_inhibition_data)| CYP | \(K_{i}\) (µM) | \(K_{i,u}\) (µM) | \(R_1\) | risk (hepatic) | \(R_{1,gut}\) | risk (intestinal) |
|---|---|---|---|---|---|---|
| CYP1A2 | NA | NA | NA | NA | NA | NA |
| CYP2B6 | NA | NA | NA | NA | NA | NA |
| CYP2C8 | 11.0 | 11.0 | 1.015 | FALSE | NA | NA |
| CYP2C9 | 13.5 | 13.5 | 1.012 | FALSE | NA | NA |
| CYP2C19 | 15.0 | 15.0 | 1.011 | FALSE | NA | NA |
| CYP2D6 | NA | NA | NA | NA | NA | NA |
| CYP3A4 | 12.5 | 12.5 | 1.013 | FALSE | 293.3 | TRUE |
Risk for direct CYP inhibition by examplinib (basic model)
See also: kinetic_cyp_induction_risk_table(), mech_stat_cyp_risk_table(), basic_ugt_inhibition_risk_table(), transporter_inhibition_risk_table()
Full DDI perpetrator report
As an easy starting point for your own full DDI perpetrator report, load the sample DDI report from the package source or github, replace the compound-specific data with the data for your drug, and knit() to a Word or pdf document.
Full documentation for ddir can be found together with the source code on github.