Functions for the calculation and documentation of the potential of drugs to act as precipitants 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 precipitant DDI risk for direct CYP inhibition (basic method). All are provided as markdown-formatted output tables:
p <- examplinib
print(p)| parameter | value | source |
|---|---|---|
| oral | 1 | |
| \(MW\) (g/mol) | 492.6 | |
| \(dose\) (mg) | 450 | |
| \(solubility\) (mg/l) | Inf | |
| \(C_{max,ss}\) (ng/ml) | 3530 | |
| \(f_u\) | 0.023 | |
| \(f_{u,mic}\) | 1 | |
| \(R_B\) | 1 | |
| \(F_a\) | 0.81 | |
| \(F_g\) | 1 | |
| \(k_a\) (1/min) | 0.00267 |
Precipitant compound parameters for examplinib
print(examplinib_cyp_inhibition)| object | ki | source |
|---|---|---|
| CYP1A2 | NA | |
| CYP2B6 | NA | |
| CYP2C8 | 11.00 | study 001 |
| CYP2C9 | 0.60 | study 001 |
| CYP2C19 | 0.25 | study 001 |
| CYP2D6 | NA | |
| CYP3A4 | 12.50 | study 001 |
In vitro inhibition data for precipitant examplinib
print(basic_cyp_inhibition_risk(p, examplinib_cyp_inhibition))| object | ki | kiu | source | r | risk_hep | r_gut | risk_intest |
|---|---|---|---|---|---|---|---|
| CYP1A2 | NA | NA | NA | NA | NA | NA | NA |
| CYP2B6 | NA | NA | NA | NA | NA | NA | NA |
| CYP2C8 | 11.00 | 11.00 | study 001 | 0.01 | FALSE | NA | NA |
| CYP2C9 | 0.60 | 0.60 | study 001 | 0.27 | TRUE | NA | NA |
| CYP2C19 | 0.25 | 0.25 | study 001 | 0.66 | TRUE | NA | NA |
| CYP2D6 | NA | NA | NA | NA | NA | NA | NA |
| CYP3A4 | 12.50 | 12.50 | study 001 | 0.01 | FALSE | 292.3264 | TRUE |
Direct CYP inhibition risk for examplinib
See also: kinetic_cyp_induction_risk(), mech_stat_cyp_risk(), basic_ugt_inhibition_risk(), transporter_inhibition_risk()
Full documentation for ddir can be found together with the source code on github.