calc_analytic_css_3comp2 {httk} | R Documentation |
Calculate the analytic steady state concentration for model 3compartment
Description
This function calculates the analytic steady state plasma or blood
concentrations as a result of constant oral infusion dosing.
The three compartment model (Pearce et al. 2017)
describes the amount of chemical in
three key tissues of the body: the liver, the portal vein (essentially, oral absorption
from the gut), and a systemic compartment ("sc") representing the rest of the body.
See solve_3comp
for additional details. The analytical
steady-state solution for the the three compartment model is:
C^{ss}_{plasma} = \frac{dose}{f_{up}*Q_{GFR} + Cl_{h} + \frac{Cl_{h}}{Q_{l}}\frac{f_{up}}{R_{b:p}}Q_{GFR}}
C^{ss}_{blood} = R_{b:p}*C^{ss}_{plasma}
where Q_GFR is the glomerular filtration rate in the kidney, Q_l is the total liver blood flow (hepatic artery plus total vein), 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.
Usage
calc_analytic_css_3comp2(
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,
route = "oral",
restrictive.clearance = TRUE,
bioactive.free.invivo = FALSE,
Caco2.options = list(),
exhalation = TRUE,
...
)
Arguments
chem.name |
Either the chemical name, CAS number, or the parameters must be specified. |
chem.cas |
Either the chemical name, CAS number, or the parameters must be specified. |
dtxsid |
EPA's 'DSSTox Structure ID (https://comptox.epa.gov/dashboard) the chemical must be identified by either CAS, name, or DTXSIDs |
parameters |
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. |
dosing |
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 |
Hourly dose rate mg/kg BW/h. |
dose.units |
The units associated with the dose received. |
concentration |
Desired concentration type, 'blood' or default 'plasma'. |
suppress.messages |
Whether or not the output message is suppressed. |
recalc.blood2plasma |
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. |
tissue |
Desired tissue conentration (defaults to whole body concentration.) |
route |
Route of exposure ("inhalation" or [DEFAULT] "oral"). |
restrictive.clearance |
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). |
bioactive.free.invivo |
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 |
Caco2.options |
A list of options to use when working with Caco2 apical to
basolateral data |
exhalation |
A Boolean (TRUE/FALSE) indicating whether exhalation is included as a route of potential clearance (Defaults to TRUE). |
... |
Additional parameters passed to parameterize function if parameters is NULL. |
Value
Steady state plasma concentration in mg/L units
Author(s)
Robert Pearce and John Wambaugh
References
Pearce RG, Setzer RW, Strope CL, Wambaugh JF, Sipes NS (2017). “Httk: R package for high-throughput toxicokinetics.” Journal of Statistical Software, 79(4), 1. doi:10.18637/jss.v079.i04.