calc_fbio.oral {httk} | R Documentation |
Functions for calculating the bioavaialble fractions from oral doses
Description
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 Yang et al. (2007).
These functions calculate the fraction absorbed (calc_fabs.oral –
S Darwich et al. (2010) and
Yu and Amidon (1999)), 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
Absorption rate is calculated according to Fick's law
(LennernÄs (1997)) assuming low blood
concentrations.
Usage
calc_fbio.oral(
parameters = NULL,
chem.cas = NULL,
chem.name = NULL,
dtxsid = NULL,
species = "Human",
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_peff(
parameters = NULL,
chem.cas = NULL,
chem.name = NULL,
dtxsid = NULL,
species = "Human",
suppress.messages = FALSE,
Caco2.Pab = NULL,
parameterize.args.list = list()
)
calc_kgutabs(
parameters = NULL,
chem.cas = NULL,
chem.name = NULL,
dtxsid = NULL,
species = "Human",
suppress.messages = FALSE,
parameterize.args.list = list()
)
calc_fgut.oral(
parameters = NULL,
chem.cas = NULL,
chem.name = NULL,
dtxsid = NULL,
species = "Human",
suppress.messages = FALSE,
Caco2.Pab.default = 1.6,
parameterize.args.list = list()
)
Arguments
parameters |
(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 |
chem.cas |
(Character) Chemical CAS number. (Defaults to 'NULL'.) (Note: Either the chemical name, CAS number, or EPA's DSSTox Structure ID must be specified). |
chem.name |
(Character) Chemical name. (Defaults to 'NULL'.) (Note: Either the chemical name, CAS number, or EPA's DSSTox Structure ID must be specified). |
dtxsid |
(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). |
species |
(Character) Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human"). |
suppress.messages |
(Logical) Whether or not the output message is suppressed. (Defaults to 'FALSE'.) |
... |
Additional parameters passed to parameterize function if parameters is NULL. |
Caco2.Pab.default |
(Numeric) Caco2 apical to basolateral data. (Defaults to 1.6.) (Not applicable for 'calc_fbio.oral'.) |
Caco2.Pab |
(Numeric) Caco2 apical to basolaterial permeability used by calc_peff |
parameterize.args.list |
List of arguments passed to |
Details
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}
).
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
).
Value
fbio.oral |
Oral bioavailability, the fraction of oral dose reaching systemic distribution in the body. |
fabs.oral |
Fraction of dose absorbed, i.e. the fraction of the dose that enters the gutlumen. |
fgut.oral |
Fraction of chemical surviving first pass metabolism in the gut. |
fhep.oral |
Fraction of chemical surviving first pass hepatic clearance. |
kgutabs |
Rate of absorption from gut (1/h). |
Functions
-
calc_fabs.oral()
: Calculate the fraction absorbed in the gut (Darwich et al., 2010) -
calc_peff()
: Calculate the effective gut permeability rate (10^-4 cm/s) -
calc_kgutabs()
: Calculate the gut absorption rate (1/h) -
calc_fgut.oral()
: Calculate the fraction of chemical surviving first pass metabolism in the gut
Author(s)
Gregory Honda and John Wambaugh
References
S Darwich A, Neuhoff S, Jamei M, Rostami-Hodjegan A (2010). “Interplay of metabolism and transport in determining oral drug absorption and gut wall metabolism: a simulation assessment using the 'Advanced Dissolution, Absorption, Metabolism (ADAM)' model.” Current drug metabolism, 11(9), 716–729. doi:10.2174/138920010794328913.
Yang J, Jamei M, Yeo KR, Tucker GT, Rostami-Hodjegan A (2007). “Prediction of intestinal first-pass drug metabolism.” Current drug metabolism, 8(7), 676–684. doi:10.2174/138920007782109733.
Honda GS, Kenyon EM, Davidson-Fritz S, Dinallo R, El Masri H, Korol-Bexell E, Li L, Angus D, Pearce RG, Sayre RR, others (2025). “Impact of gut permeability on estimation of oral bioavailability for chemicals in commerce and the environment.” ALTEX-Alternatives to animal experimentation, 42(1), 56–74. doi:10.14573/altex.2403271.
Yu LX, Amidon GL (1999). “A compartmental absorption and transit model for estimating oral drug absorption.” International journal of pharmaceutics, 186(2), 119–125. doi:10.1016/S0378-5173(99)00147-7.
LennernĂ„s H (1997). “Human jejunal effective permeability and its correlation with preclinical drug absorption models.” Journal of Pharmacy and Pharmacology, 49(7), 627–638. doi:10.1111/j.2042-7158.1997.tb06084.x.