parameterize_fetal_pbtk {httk}

Parameterize_fetal_PBTK

Description

This function initializes the parameters needed in the functions solve_fetal_pbtk by calling solve_pbtk and adding additional parameters.

Usage

parameterize_fetal_pbtk(
  chem.cas = NULL,
  chem.name = NULL,
  dtxsid = NULL,
  species = "Human",
  fetal_fup_adjustment = TRUE,
  return.kapraun2019 = TRUE,
  suppress.messages = FALSE,
  ...
)

Arguments

chem.cas

Either the chemical name or the CAS number must be specified.

chem.name

Either the chemical name or the CAS number 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

species

Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human"). Currently only a narrow human model is supported.

fetal_fup_adjustment

Logical indicator of whether to use an adjusted estimate for fetal fup based on the fetal:maternal plasma protein binding ratios presented in McNamara and Alcorn's 2002 study "Protein Binding Predictions in Infants." Defaults to TRUE.

return.kapraun2019

If TRUE (default) the empirical parameters for the Kapraun et al. (2019) maternal-fetal growth parameters are provided.

suppress.messages

Whether or not the output message is suppressed.

...

Arguments passed to parameterize_pbtk.

Value

pre_pregnant_BW

Body Weight before pregnancy, kg.

Clmetabolismc

Hepatic Clearance, L/h/kg BW.

Fabsgut

Fraction of the oral dose absorbed, i.e. the fraction of the dose that enters the gutlumen.

Funbound.plasma

Fraction of plasma that is not bound.

Fhep.assay.correction

The fraction of chemical unbound in hepatocyte assay using the method of Kilford et al. (2008)

hematocrit

Percent volume of red blood cells in the blood.

Kgut2pu

Ratio of concentration of chemical in gut tissue to unbound concentration in plasma.

kgutabs

Rate that chemical enters the gut from gutlumen, 1/h.

Kkidney2pu

Ratio of concentration of chemical in kidney tissue to unbound concentration in plasma.

Kliver2pu

Ratio of concentration of chemical in liver tissue to unbound concentration in plasma.

Klung2pu

Ratio of concentration of chemical in lung tissue to unbound concentration in plasma.

Krbc2pu

Ratio of concentration of chemical in red blood cells to unbound concentration in plasma.

Krest2pu

Ratio of concentration of chemical in rest of body tissue to unbound concentration in plasma.

million.cells.per.gliver

Millions cells per gram of liver tissue.

MW

Molecular Weight, g/mol.

Qgfrc

Glomerular Filtration Rate, L/h/kg BW^3/4, volume of fluid filtered from kidney and excreted.

Rblood2plasma

The ratio of the concentration of the chemical in the blood to the concentration in the plasma from available_rblood2plasma.

Vgutc

Volume of the gut per kg body weight, L/kg BW.

Vkidneyc

Volume of the kidneys per kg body weight, L/kg BW.

Vliverc

Volume of the liver per kg body weight, L/kg BW.

Vlungc

Volume of the lungs per kg body weight, L/kg BW.

Vthyroidc

Volume of the thyroid per kg body weight, L/kg BW.

Kfgut2pu

Ratio of concentration of chemical in fetal gut tissue to unbound concentration in plasma.

Kfkidney2pu

Ratio of concentration of chemical in fetal kidney tissue to unbound concentration in plasma.

Kfliver2pu

Ratio of concentration of chemical in fetal liver tissue to unbound concentration in plasma.

Kflung2pu

Ratio of concentration of chemical in fetal lung tissue to unbound concentration in plasma.

Kfrest2pu

Ratio of concentration of chemical in fetal rest of body tissue to unbound concentration in plasma.

Kfbrain2pu

Ratio of concentration of chemical in fetal brain tissue to unbound concentration in plasma.

Kthyroid2pu

Ratio of concentration of chemical in fetal thyroid tissue to unbound concentration in plasma.

Kfthyroid2pu

Ratio of concentration of chemical in fetal thyroid tissue to unbound concentration in plasma.

Kplacenta2pu

Ratio of concentration of chemical in placental tissue to unbound concentration in maternal plasma.

Kfplacenta2pu

Ratio of concentration of chemical in placental tissue to unbound concentration in fetal plasma.

Author(s)

Robert Pearce, Mark Sfeir, John Wambaugh, and Dustin Kapraun

Mark Sfeir, Dustin Kapraun, John Wambaugh

References

Kilford PJ, Gertz M, Houston JB, Galetin A (2008). “Hepatocellular binding of drugs: correction for unbound fraction in hepatocyte incubations using microsomal binding or drug lipophilicity data.” Drug Metabolism and Disposition, 36(7), 1194–1197.

McNamara PJ, Alcorn J. Protein binding predictions in infants. AAPS PharmSci. 2002;4(1):E4. doi: 10.1208/ps040104. PMID: 12049488.

See Also

solve_fetal_pbtk

parameterize_pbtk

predict_partitioning_schmitt

apply_clint_adjustment

tissue.data

physiology.data

kapraun2019

Examples

 parameters <- parameterize_fetal_pbtk(chem.cas='80-05-7')

 parameters <- parameterize_fetal_pbtk(chem.name='Bisphenol-A',species='Rat')