These functions calculate the fraction of chemical absorbed from the gut
based upon in vitro measured Caco-2 membrane permeability data.
Caco-2 permeabilities (\(10^{-6}\) cm/s) are related to
effective permeability based on yang2007prediction;textualhttk.
These functions calculate the fraction absorbed (calc_fabs.oral --
darwich2010interplay;textualhttk), the fraction
surviving first pass gut metabolism (calc_fgut.oral), and the overall systemic
oral bioavailability
(calc_fbio.oral). Note that the first pass hepatic clearance is calculated within the
parameterization and other functions. using calc_hep_bioavailability
We assume that systemic oral bioavailability (\(F_{bio}\))
consists of three components:
(1) the fraction of chemical absorbed from intestinal lumen into enterocytes
(\(F_{abs}\)),
(2) the fraction surviving intestinal metabolism
(\(F_{gut}\)), and
(3) the fraction surviving first-pass hepatic metabolism
(\(F_{hep}\)). This function returns (\(F_{abs}*F_{gut}\)).
calc_fbio.oral(
parameters = NULL,
chem.cas = NULL,
chem.name = NULL,
dtxsid = NULL,
species = "Human",
default.to.human = FALSE,
suppress.messages = FALSE
)calc_fabs.oral(
parameters = NULL,
chem.cas = NULL,
chem.name = NULL,
dtxsid = NULL,
species = "Human",
suppress.messages = FALSE,
Caco2.Pab.default = 1.6
)
calc_fgut.oral(
parameters = NULL,
chem.cas = NULL,
chem.name = NULL,
dtxsid = NULL,
species = "Human",
default.to.human = FALSE,
suppress.messages = FALSE,
Caco2.Pab.default = 1.6
)
Oral bioavailability, the fraction of oral dose reaching systemic distribution in the body.
Fraction of dose absorbed, i.e. the fraction of the dose that enters the gutlumen.
Fraction of chemical surviving first pass metabolism in the gut.
Fraction of chemical surviving first pass hepatic clearance.
(List) A list of the parameters (Caco2.Pab, Funbound.Plasma, Rblood2plasma,
Clint, BW, Qsmallintestine, Fabs, Fgut) used in the calculation, either supplied by user
or calculated in parameterize_steadystate.
(Character) Chemical CAS number. (Defaults to `NULL`.) (Note: Either the chemical name, CAS number, or EPA's DSSTox Structure ID must be specified).
(Character) Chemical name. (Defaults to `NULL`.) (Note: Either the chemical name, CAS number, or EPA's DSSTox Structure ID must be specified).
(Character) EPA's DSSTox Structure ID (https://comptox.epa.gov/dashboard). (Defaults to `NULL`.) (Note: Either the chemical name, CAS number, or EPA's DSSTox Structure ID must be specified).
(Character) Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").
(Logical) Substitutes missing rat values with human values if TRUE. (Not applicable for `calc_fabs.oral`.) (Defaults to `FALSE`.)
(Logical) Whether or not the output message is suppressed. (Defaults to `FALSE`.)
(Numeric) Caco2 apical to basolateral data. (Defaults to 1.6.) (Not applicable for `calc_fbio.oral`.)
calc_fabs.oral(): Calculate the fraction absorbed in the gut (Darwich et al., 2010)
calc_fgut.oral(): Calculate the fraction of chemical surviving first pass metabolism in the gut
Gregory Honda
We model systemic oral bioavailability as
\(F_{bio}=F_{abs}*F_{gut}*F_{hep}\).
\(F_{hep}\) is estimated from in vitro TK data using
calc_hep_bioavailability.
If \(F_{bio}\) has been measured in vivo and is found in
table chem.physical_and_invitro.data then we set
\(F_{abs}*F_{gut}\) to the measured value divided by \(F_{hep}\).
Otherwise, if Caco2 membrane permeability data or predictions
are available \(F_{abs}\) is estimated using calc_fgut.oral.
Intrinsic hepatic metabolism is used to very roughly estimate (\(F_{gut}\))
using calc_fgut.oral.
If argument keepit100 is used then there is complete absorption from the gut
(that is, \(F_{abs}=F_{gut}=1\)).
darwich2010interplayhttk yang2007predictionhttk HondaUnpublishedCaco2httk