This function calculates the steady state plasma or venous blood concentrations as a result of constant oral infusion dosing. The equation, initally used for high throughput in vitro-in vivo extrapolation in rotroff2010incorporatinghttk and later given in wetmore2012integrationhttk, assumes that the concentration is the inverse of the total clearance, which is the sum of hepatic metabolism and renal filatrion: $$C^{ss}_{plasma} = \frac{dose}{f_{up}*Q_{GFR}+Cl_{h}}$$ $$C^{ss}_{blood} = R_{b:p}*C^{ss}_{plasma}$$ where Q_GFR is the glomerular filtration rate in the kidney, Cl_h is the chemical-specific whole liver metabolism clearance (scaled up from intrinsic clearance, which does not depend on flow), f_up is the chemical-specific fraction unbound in plasma, R_b:p is the chemical specific ratio of concentrations in blood:plasma.
calc_analytic_css_3compss(
chem.name = NULL,
chem.cas = NULL,
dtxsid = NULL,
parameters = NULL,
dosing = list(daily.dose = 1),
hourly.dose = NULL,
dose.units = "mg",
concentration = "plasma",
suppress.messages = FALSE,
recalc.blood2plasma = FALSE,
tissue = NULL,
restrictive.clearance = TRUE,
bioactive.free.invivo = FALSE,
Caco2.options = list(),
...
)Steady state plasma concentration in mg/L units
Either the chemical name, CAS number, or the parameters must be specified.
Either the chemical name, CAS number, or the parameters must be specified.
EPA's 'DSSTox Structure ID (https://comptox.epa.gov/dashboard) the chemical must be identified by either CAS, name, or DTXSIDs
Chemical parameters from parameterize_pbtk (for model = 'pbtk'), parameterize_3comp (for model = '3compartment), parameterize_1comp(for model = '1compartment') or parameterize_steadystate (for model = '3compartmentss'), overrides chem.name and chem.cas.
List of dosing metrics used in simulation, which includes the namesake entries of a model's associated dosing.params. For steady-state calculations this is likely to be either "daily.dose" for oral exposures or "Cinhaled" for inhalation.
Hourly dose rate mg/kg BW/h.
The units associated with the dose received.
Desired concentration type, 'blood' or default 'plasma'.
Whether or not the output message is suppressed.
Recalculates the ratio of the amount of chemical in the blood to plasma using the input parameters. Use this if you have 'altered hematocrit, Funbound.plasma, or Krbc2pu.
Desired tissue concentration (defaults to whole body concentration.)
If TRUE (default), then only the fraction of chemical not bound to protein is available for metabolism in the liver. If FALSE, then all chemical in the liver is metabolized (faster metabolism due to rapid off-binding).
If FALSE (default), then the total concentration is treated as bioactive in vivo. If TRUE, the the unbound (free) plasma concentration is treated as bioactive in vivo. Only works with tissue = NULL in current implementation.
A list of options to use when working with Caco2 apical to
basolateral data Caco2.Pab, default is Caco2.options = list(Caco2.Pab.default = 1.6,
Caco2.Fabs = TRUE, Caco2.Fgut = TRUE, overwrite.invivo = FALSE, keepit100 = FALSE). Caco2.Pab.default sets the default value for
Caco2.Pab if Caco2.Pab is unavailable. Caco2.Fabs = TRUE uses Caco2.Pab to calculate
fabs.oral, otherwise fabs.oral = Fabs. Caco2.Fgut = TRUE uses Caco2.Pab to calculate
fgut.oral, otherwise fgut.oral = Fgut. overwrite.invivo = TRUE overwrites Fabs and Fgut in vivo values from literature with
Caco2 derived values if available. keepit100 = TRUE overwrites Fabs and Fgut with 1 (i.e. 100 percent) regardless of other settings.
See get_fbio for further details.
Additional parameters passed to parameterize function if parameters is NULL.
Robert Pearce and John Wambaugh
This equation is a simplification of the steady-state plasma concentration
in the three-comprtment model (see solve_3comp), neglecting a
higher order term that causes this Css to be higher for very rapidly cleared
chemicals.
calc_analytic_css
parameterize_steadystate