get_invitroPK_param

This function retrieves in vitro PK data (for example, intrinsic metabolic clearance 
or fraction unbound in plasma) for the the chemical specified by argument "chem.name", "dtxsid", 
or chem.cas from the table <code>chem.physical_and_invitro.data</code>.
This function looks for species-specific values based on the argument "species".

Pre-made models that can be rapidly tailored to various chemicals
and species using chemical-specific in vitro data and physiological
information. These tools allow incorporation of chemical
toxicokinetics ("TK") and in vitro-in vivo extrapolation ("IVIVE")
into bioinformatics, as described by Pearce et al. (2017)
(<doi:10.18637/jss.v079.i04>). Chemical-specific
in vitro data characterizing toxicokinetics have been obtained
from relatively high-throughput experiments. The
chemical-independent ("generic") physiologically-based ("PBTK") and empirical
(for example, one compartment) "TK" models included here can be
parameterized with in vitro data or in silico predictions which are
provided for thousands of chemicals, multiple exposure routes,
and various species. High throughput toxicokinetics ("HTTK") is the
combination of in vitro data and generic models. We establish the
expected accuracy of HTTK for chemicals without in vivo data
through statistical evaluation of HTTK predictions for chemicals
where in vivo data do exist. The models are systems of ordinary
differential equations that are developed in MCSim and solved
using compiled (C-based) code for speed. A Monte Carlo sampler is
included for simulating human biological variability
(Ring et al., 2017 <doi:10.1016/j.envint.2017.06.004>)
and propagating parameter uncertainty
(Wambaugh et al., 2019 <doi:10.1093/toxsci/kfz205>).
Empirically calibrated methods are included for predicting
tissue:plasma partition coefficients and volume of distribution
(Pearce et al., 2017 <doi:10.1007/s10928-017-9548-7>).
These functions and data provide a set of tools for using IVIVE to
convert concentrations from high-throughput screening experiments
(for example, Tox21, ToxCast) to real-world exposures via reverse
dosimetry (also known as "RTK")
(Wetmore et al., 2015 <doi:10.1093/toxsci/kfv171>).

John Wambaugh

httk

High-Throughput Toxicokinetics

Sarah Davidson-Fritz

Robert Pearce

Caroline Ring

Greg Honda

Mark Sfeir

Matt Linakis

Dustin Kapraun

Nathan Pollesch

Miyuki Breen

Shannon Bell

Xiaoqing Chang

Todor Antonijevic

Jimena Davis

Elaina Kenyon

Katie Paul Friedman

Celia Schacht

Meredith Scherer

James Sluka

Noelle Sinski

Nisha Sipes

Barbara Wetmore

Lily Whipple

Woodrow Setzer

get_invitroPK_param function

<dl><dt>param</dt>
<dd>The desired parameters, a vector or single value.</dd>
<dt>species</dt>
<dd>Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or
default "Human").</dd>
<dt>chem.name</dt>
<dd>The chemical names that you want parameters for, a vector or single value</dd>
<dt>chem.cas</dt>
<dd>The chemical CAS numbers that you want parameters for, a vector or single value</dd>
<dt>dtxsid</dt>
<dd>EPA's 'DSSTox Structure ID (https://comptox.epa.gov/dashboard)</dd></dl>

Arguments

Author

Retrieve species-specific in vitro data from chem.physical_and_invitro.data table — get_invitroPK_param

<dl>

<dt>param</dt>
<dd>The desired parameters, a vector or single value.</dd>


<dt>species</dt>
<dd>Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or
default "Human").</dd>


<dt>chem.name</dt>
<dd>The chemical names that you want parameters for, a vector or single value</dd>


<dt>chem.cas</dt>
<dd>The chemical CAS numbers that you want parameters for, a vector or single value</dd>


<dt>dtxsid</dt>
<dd>EPA's 'DSSTox Structure ID (https://comptox.epa.gov/dashboard)</dd>

</dl>

Retrieve species-specific in vitro data from chem.physical_and_invitro.data table

Parameter	Description	Units
[SPECIES].Clint	(Primary hepatocyte suspension) intrinsic hepatic clearance. Entries with comma separated values are Bayesian estimates of the Clint distribution - displayed as the median, 95th credible interval (that is quantile 2.5 and 97.5, respectively), and p-value.	uL/min/10^6 hepatocytes
[SPECIES].Clint.pValue	Probability that there is no clearance observed. Values close to 1 indicate clearance is not statistically significant.	none
[SPECIES].Caco2.Pab	Caco-2 Apical-to-Basal Membrane Permeability	10^-6 cm/s
[SPECIES].Fabs	In vivo measured fraction of an oral dose of chemical absorbed from the gut lumen into the gut	unitless fraction
[SPECIES].Fgut	In vivo measured fraction of an oral dose of chemical that passes gut metabolism and clearance	unitless fraction
[SPECIES].Foral	In vivo measued fractional systemic bioavailability of an oral dose, modeled as he product of Fabs * Fgut * Fhep (where Fhep is first pass hepatic metabolism).	unitless fraction
[SPECIES].Funbound.plasma	Chemical fraction unbound in presence of plasma proteins (fup). Entries with comma separated values are Bayesian estimates of the fup distribution - displayed as the median and 95th credible interval (that is quantile 2.5 and 97.5, respectively).	unitless fraction
[SPECIES].Rblood2plasma	Chemical concentration blood to plasma ratio	unitless ratio

get_invitroPK_param: Retrieve species-specific in vitro data from chem.physical_and_invitro.data table

Description

Usage

Value

Arguments

Author

Details

See Also