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@jfwambaugh jfwambaugh released this 13 Feb 18:32
· 339 commits to main since this release
v2.3.0
398fac3

This version accompanies the submission of manuscript Honda et al. "Impact of Gut Permeability on Estimation of Oral Bioavailability for Chemicals in Commerce and the Environment". Find the analysis scripts on GitHub

Bug Fixes

  • Added parameter plasma.vol to one compartment model so that Monte Carlo works for non-human species
  • Added default units for Aexh and Ainh state variables in gas_pbtk model so that calc_css works for accumulative chemcials
  • Corrected the Linakis et al. (2020) vignette to reflect that all CvTdb data used there already are in uM
  • Corrected ppbv unit conversions in convert_units
  • Precision of time output in solve_model is no longer restricted to four significant figures
  • Fixed bug with Monte Carlo functions (for example, calc_mc_oral_equiv) wherein you could not specify the argument parameters to be a table created by create_mc_samples (thanks Jayme Coyle and Tyler Lalonde)
  • Revised convert_units to handle multiple molecular weights -- this enables convert_mc_oral_equivalent to take a table of parameters for Monte Carlo
  • Updated the checks and reported error messages in get_clint and get_invtroPK_param to be more informative
  • Corrected calculation of mean blood:plasma partition coefficient when measured RBlood2plasma is avaialble
  • Clint and fup are now adjusted for in vitro binding when invitrouv=FALSE (thanks cm16120)

New Features

  • Added in vitro measured Caco-2 membrane permeability data for 310 chemicals allowing characterization of oral bioavailability
  • Added new function load_honda2023 to load QSPR (quantitative structure-property relationship model) predictions for Caco-2 membrane permeability for ~10,000 chemicals -- QSPR is optimized to detect low permeability chemicals and therefore predicts only three values (low/medium/high permeability)
  • Added new functions calc_fbio.oral, calc_fabs.oral, and calc_fgut.oral for calculating systemic bioavailability as Fbio = Fabs * Fgut * Fhep where first-pass hepatic metabolism was already available from calc_hep_bioavailability.
  • Changed the name of the variable describing fraction absorbed from the gut prior to first-pass hepatic metabolism to Fabsgut to reflect that Fabs and Fgut are now modeled separately (that is, Fabsgut = Fabs * Fgut).
  • Integrated Fabs and Fgut into oral exposure for all TK models and integrated into population variability and uncertainty functions within invitro_uv
  • Added new function benchmark_httk to compare current function of the package against historical performance (stored in data.frame httk.performance)
  • We now skip over the first five minutes when calculating Cmax in calc_tkstats to allow PBTK model to distribute iv doses

Enhancements

  • Added QSPR predictions for Fup and Clint for several thousand chemicals using the Dawson et al. (2020) models -- accessible from load_dawson2021 (thank you Alex Fisher and Mike Tornero!)
  • Predicted phys-chem properties for most chemicals using OPERA v2.9 (updated armitage_eval to properly convert water solubility from OPERA units)
  • Package now requires ggplot2 -- will gradually shift all plotting from base R
  • Returned and updated the Pearce et al. (2017) vignette on Evaluation of Tissue Partitioning
  • Revised function convert_units, expanding the variety of unit conversions available -- it is critical to distringuish between state of matter (liquid vs. gas)
  • Model 1compartment allows volatile chemicals again since clearance is amorphous for that model (likely underestimated without exhalation)
  • Many manuscript references listed in function documentation were converted to a BibTex format from manual insertion of the citations. (thanks Lily Whipple)
  • Updated get_physchem_param to be case-insensitive
  • New Clint and Fup data curated from literature by ICF from Black et al. (2021), Williamson et al. (2020), Zanelli et al. (2012), Yamagata et al. (2017), and Zanelli et al. (2019) (thank you Noelle Sinski and Colin Guider)
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