calc_fbio.oral {httk} | R Documentation |
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.
calc_fbio.oral(
parameters = NULL,
chem.cas = NULL,
chem.name = NULL,
dtxsid = NULL,
species = "Human",
default.to.human = FALSE,
suppress.messages = FALSE,
restrictive.clearance = 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",
default.to.human = FALSE,
suppress.messages = FALSE,
Caco2.Pab = NULL
)
calc_kgutabs(
parameters = NULL,
chem.cas = NULL,
chem.name = NULL,
dtxsid = NULL,
species = "Human",
default.to.human = FALSE,
suppress.messages = FALSE
)
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
)
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"). |
default.to.human |
(Logical) Substitutes missing rat values with human values if TRUE. (Not applicable for 'calc_fabs.oral'.) (Defaults to 'FALSE'.) |
suppress.messages |
(Logical) Whether or not the output message is suppressed. (Defaults to 'FALSE'.) |
restrictive.clearance |
Protein binding not taken into account (set to 1) in liver clearance if FALSE. |
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 |
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
).
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). |
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
Gregory Honda and John Wambaugh
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. 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. Honda G, Kenyon EM, Davidson-Fritz SE, Dinallo R, El-Masri H, Korel-Bexell E, Li L, Paul-Friedman K, Pearce R, Sayre R, Strock C, Thomas R, Wetmore BA, Wambaugh JF (2023). “Impact of Gut Permeability on Estimation of Oral Bioavailability for Chemicals in Commerce and the Environment.” Unpublished. Yu LX, Amidon GL (1999). “A compartmental absorption and transit model for estimating oral drug absorption.” International journal of pharmaceutics, 186(2), 119–125. 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.