calc_analytic_css_3comp: Calculate the analytic steady state concentration for model...

In httk: High-Throughput Toxicokinetics

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 \insertCitepearce2017httkhttk 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_3comp(
  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(),
  ...
)

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.)
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 tissue = NULL in current implementation.
Caco2.options	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.

Value

Steady state plasma concentration in mg/L units

Author(s)

Robert Pearce and John Wambaugh

References

\insertAllCited

See Also

calc_analytic_css

parameterize_3comp

httk documentation built on Sept. 11, 2024, 9:32 p.m.