News for R package httk

Changes in version 1.8

This version is consistent with the published version of Pearce et al. "Evaluation and calibration of high-throughput predictions of chemical distribution to tissues",
thus containing new regressions added for partition coefficient calibration without Funbound.plasma adjustment with 
separate arguments for using regressions (regression) and adjusted Funbound.plasma (adjusted.Funbound.plasma).
Data from ADMET used in Sipes et al. (2017) is now included as Sipes2017 and can be added with the new function: load_sipes2017().
Separate options have been added for the regressions and adjusted Funbound.plasma.
New data has been added from an IVIVE evaluation of toxicokinetics (Wambaugh et al. 2018).
Funbound.plasma values from Wetmore 2012 and 2013 that were previously rounded to 2 decimal places are now rounded to 3,
adding additional compounds that were otherwise assumed to be below the limit of detection.
pKa data is now readable when values are separated by a semicolon rather than a comma. These values were previously
misread as neutral.
Partition coefficients can now be predicted without calculating all of them, using the tissues argument.
Calc_mc_css runs faster when not using httkpop and calculating Rblood2plasma, now only calculated once.
New data are added to chem.invivo.PK.data and chem.invivo.PK.summary.data.
chem.lists is updated, and is.pharma has been added as a function.
A new table is included: chem.invivo.PK.aggregate data
calc_mc_css bug fix: daily.dose now working as an argument (previously only running as 1).
calc_analytic_css does not recalculate all partition coefficients when specifying a tissue.
logP values from EPISuite or valued NA have been replaced with predictions from OPERA where available. 
hepatic.bioavailability is added as a parameter to the models 1compartment (parameterize_1comp) and 3compartmentss (parameterize_steadystate)
and now used with these models (multiplied by the dose and Fgutabs).
kinhabs and kdermabs, both of which were unused in the models, are removed.
vLiverPBPK.c, the source file for the pbtk model, now has updated variable names, and corresponding changes are made in solve_pbtk.
The time step immediately after addition of dose is added to better capture peak concentration for iv dosing.
kgutabs default changed to 2.18.



Changes in version 1.7

This revision is consistent with the JSS publication of Pearce et al. "httk: R Package for High-Throughput Toxicokinetics".
Minor bug fixes include: corrected intrinsic clearances for (about 10) compounds from Brown 2007, fixed output message from calc_mc_css
Corrected Funbound.plasma used for predicting partitioning into interstitial protein (negligible difference in predictions)
Fixed bug in calculating Rblood2plasma in calc_mc_css, and added faster method for calculating Rblood2plasma for 3compartmentss.

changes in version 1.6

This revision includes data and modifications as reported in the recently submitted Pearce et al. paper 
"Evaluation and Calibration of High‐Throughput Predictions of Chemical Distribution to Tissues". 
The Schmitt (2008) method for partition coefficients has been modified and calibrated using experimental data. 
The new method is now default, although the previous approach is available (set regression=FALSE and Funbound.plasma.pc.correction=FALSE
for other models).  The membrane affinity regression is new and always used in place of the old. 

added functions: available_rblood2plasma
in vivo Rblood2plasma used when available
well-stirred blood correction and restrictive.clearance options added 
New in vitro data from Uchimura 2010, brown 2007 and Pirovano 2016, Gulden 2002
Tonnelier Funbound.plasma values of 0.005 changed to 0 in chem.physical_and_invitro.data
new tissue.data table with Ruark 2014 that contains different formatting with human and rat specific data
parameterize_schmitt: added force.human.fub argument
added plasma protein and neutral lipid volume fractions to physiology.data for use in package
calc_mc_css: defaults to direct resampling. no longer coerces species to human when httkpop=T.  
             When another species is entered, a warning is thrown and the function behaves as if httkpop=F.
updated help file references and examples
fixed parameterize_3comp default.to.human bug: always set to false
removed temperature from schmitt parameters
overwrite 0 values for Fubound.plasma when overwrite=F in add_chemtable
added vignette for generating partition coefficient plots
added dsstox info: new columns: "DSSTox_Substance_Id","Structure_Formula", or "Substance_Type".  overwrote: MW and SMILES
added pc.data and obach2008 tables
httkpop option in calc_mc_css: well-stirred correction and new Funbound.plasma used by default.  
                               New partition coefficients used with other models by default.

Changes in version 1.5

This revision provides models, data, and vignettes for “httk-pop” functionality. “httk-pop” allows Monte Carlo simulation of physiological 
variability as described in Ring et al. “Identifying populations sensitive to environmental chemicals by simulating toxicokinetic variability”, 
which is accepted for publication at Environment International. This new human variability functionality is the new default, 
although the previous approach is available (set httkpop=FALSE).

default.to.human argument added to calc_hepatic_clearance and calc_stats.
calc_hepatic_clearance and calc_total_clearance do not necessarily require all parameters.
Argument "tissue" added to calc_analytic_css, calc_mc_css, and calc_mc_oral_equiv, enabling tissue specific calculations in addition to plasma.
get_cheminfo minor bug fix.
calc_dow: fraction neutral argument changed to fraction charged, thus treating zwitterions as neutrals
monte_carlo bug fix: Upper bound placed at limit of detection for censored params truncated normal distribution.  However, this has no impact on
                     the default case where the limit of detection is .01 the mean .005 because of the small standard deviation size (.0015). 
                     Only large coefficients of variation or Funbound.plasma values close to the limit of detection would be affected.
Multiple iv doses enabled in solve functions.
get_rblood2plasma function added to retrieve in vivo Rblood2plasma from chem.physical_and_invitro.data.

Version: 1.4
This revision incorporates changes suggested by the reviewers of Pearce et al. "httk: R Package for High-Throughput Toxicokinetics",
which was accepted, pending minor revision, in the Journal of  Statistical Software, included in vignettes. 

Table name "PK.physiology.data" changed to "physiology.data".


Version 1.3
This revision adds ~200 more chemicals (from two recent publications including Wetmore et al. 2015) and make several small changes to improve usability and stability. 

Version 1.2
This revision changes some model parameter names to follow a more systematic naming convention. 
Minor bugs have been fixed. 
This version is consistent with a newly submitted article to JSS describing use of the package. 

Version 1.1

Initial public (CRAN) release.


