Key perpetrator concentrations

This function calculates the relevant perpetrator concentrations in \(\mu M\) (default) or ng/ml for a DDI perpetrator compound.

Usage

key_concentrations(obj, qh = 1.616, qent = 18/60, molar = TRUE)

Arguments

obj

A perpetrator object.

qh

Hepatic blood flow in l/min, defaults to 1.616 l/min.

qent

Enteric blood flow in l/min, defaults to 0.3 l/min = 18 l/h.

molar

Switch to select output in molar concentrations.

Value

Key perpetrator concentrations in uM (default) or ng/ml as a named vector.

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.

See also

conc_table()

property_table()

Examples

key_concentrations(examplinib_parent)
#>         igut      imaxssu   imaxinletu   imaxintest 
#> 3654.0803898    0.1648193    0.1929384    6.5855664 
key_concentrations(examplinib_parent, molar = FALSE)
#>         igut      imaxssu   imaxinletu   imaxintest 
#> 1.800000e+06 8.119000e+01 9.504145e+01 3.244050e+03 
key_concentrations(examplinib_metabolite)
#>       igut    imaxssu imaxinletu imaxintest 
#> 0.00000000 0.02458939 0.02458939 0.02458939