Key precipitant concentrations — key_conc

Print a markdown-formatted table of the relevant precipitant concentrations in $\mu M$ and ng/ml for a DDI precipitant compound.

Usage

key_conc_table(x, signif = 3, qh = 1.616, qent = 18/60)

Arguments

x: DDI precipitant object.
signif: Number of significant places.
qh: Hepatic blood flow in L/min.
qent: Enteric blood flow in L/min.

Value

Markdown-formatted text.

Details

Gut concentration

$$I_{gut} = \frac{D} {250}$$

If the above exceeds the aqueous solubility of the drug, $I_{gut}$ is set to its solubility.

Unbound systemic concentration

$$I_{max,ss,u}=I_{max,ss} * f_u$$

Unbound hepatic inlet concentration

For orally administered (parent) compounds, the hepatic inlet concentration is the systemic concentration plus a portal term:

$$portal\ term = D*\frac{F_a*F_g*k_a}{Q_h*R_B}*1000\ ng/ml$$

where $D$ is the administered dose in mg, $F_a$ the fraction absorbed after oral administration, $F_g$ the fraction available after gut metabolism, $k_a$ the absorption rate, $Q_h$ the hepatic blood flow and $R_B$ the blood-to-plasma ratio.

The relevant hepatic inlet concentration ($I_{max,inlet,u}$, also called $I_h$ in the mechanistic static modeling equations) concentration is the sum of the maximal systemic plasma concentration and the portal contribution:

$$I_{max,inlet,u}=(I_{max,ss} + portal\ term) * f_u$$

Enteric (villous) concentration

For orally administered (parent) compounds, the villous concentration in the gut ($I_{enteric}$, also called $I_g$ in the mechanistic static modeling equations) is calculated as:

$$I_{enteric,u} = D * \frac{F_a*k_a}{Q_{ent}} *1000\ ng/ml$$

where $F_a$ is the fraction absorbed after oral administration, $k_a$ the absorption rate, $Q_{ent}$ the enteric villous blood flow and $R_B$ the blood-to-plasma distribution ratio of the compound.

Note that as per the FDA guideline (refer to FDA, 2020, Fig. 7, and Rostami-Hodjegan and Tucker, 2004) the blood-to-plasma ratio and the plasma binding of the drug are not applicable.

Examples

key_conc_table(examplinib)
#> 
#> 
#> Table: Key precipitant concentrations for examplinib
#> 
#> |parameter            | value ($ng/ml$)| value ($\mu M$)|
#> |:--------------------|---------------:|---------------:|
#> |$I_{gut}$            |        1.80e+06|        3650.000|
#> |$I_{max,ss,u}$       |        8.12e+01|           0.165|
#> |$I_{max,inlet,u}$    |        9.50e+01|           0.193|
#> |$I_{max,intestinal}$ |        3.24e+03|           6.590|