This function calculates the analytic steady state concentration (mg/L) as a result of constant oral infusion dosing. Concentrations are returned for plasma by default, but various tissues or blood concentrations can also be given as specified.
calc_analytic_css_pbtk(
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', 'tissue', 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 conentration (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
The PBTK model pearce2017httkhttk predicts the amount of chemical in various tissues of the body. A system of ordinary differential equations describes how the amounts in each tissue change as a function of time. The analytic steady-state equation was found by algebraically solving for the tissue concentrations that result in each equation being zero -- thus determining the concentration at which there is no change over time as the result of a fixed infusion dose rate.
The analytical solution is: $$C^{ss}_{ven} = \frac{dose rate * \frac{Q_{liver} + Q_{gut}}{\frac{f_{up}}{R_{b:p}}*Cl_{metabolism} + (Q_{liver}+Q_{gut})}}{Q_{cardiac} - \frac{(Q_{liver} + Q_{gut})^2}{\frac{f_{up}}{R_{b:p}}*Cl_{metabolism} + (Q_{liver}+Q_{gut})} - \frac{(Q_{kidney})^2}{\frac{f_{up}}{R_{b:p}}*Q_{GFR}+Q_{kideny}}-Q_{rest}}$$ $$C^{ss}_{plasma} = \frac{C^{ss}_{ven}}{R_{b:p}}$$ $$C^{ss}_{tissue} = \frac{K_{tissue:fuplasma}*f_{up}}{R_{b:p}}*C^{ss}_{ven}$$ where Q_cardiac is the cardiac output, Q_gfr is the glomerular filtration rate in the kidney, other Q's indicate blood flows to various tissues, Cl_metabolism is the chemical-specific whole liver metabolism clearance, f_up is the chemical-specific fraction unbound in plasma, R_b2p is the chemical specific ratio of concentrations in blood:plasma, K_tissue2fuplasma is the chemical- and tissue-specific equilibrium partition coefficient and dose rate has units of mg/kg/day.
calc_analytic_css
parameterize_pbtk