honda.ivive {httk}

Return the assumptions used in Honda et al. 2019

Description

This function returns four of the better performing sets of assumptions evaluated in Honda et al. 2019 (https://doi.org/10.1371/journal.pone.0217564).These include four different combinations of hepatic clearance assumption, in vivo bioactivity assumption, and relevant tissue assumption. Generally, this function is not called directly by the user, but instead called by setting the IVIVE option in calc_mc_oral_equiv, calc_mc_css, and calc_analytic functions. Currently, these IVIVE option is not implemented the solve_1comp etc. functions.

Usage

honda.ivive(method = "Honda1", tissue = "liver")

Arguments

method

This is set to one of "Honda1", "Honda2", "Honda3", or "Honda4".

tissue

This is only relevant to "Honda4" and indicates the relevant tissue compartment.

Details

Only four sets of IVIVE assumptions that performed well in Honda et al. (2019) are currently included: "Honda1" through "Honda4". The use of max (peak) concentration can not be currently be calculated with calc_analytic_css. The httk default settings correspond to "Honda3":

	In Vivo Conc.	Metabolic Clearance	Bioactive Chemical Conc. In Vivo	TK Statistic Used*	Bioactive Chemical Conc. In Vitro
Honda1	Veinous (Plasma)	Restrictive	Free	Mean Conc. In Vivo	Free Conc. In Vitro
Honda2	Veinous	Restrictive	Free	Mean Conc. In Vivo	Nominal Conc. In Vitro
Honda3	Veinous	Restrictive	Total	Mean Conc. In Vivo	Nominal Conc. In Vitro
Honda4	Target Tissue	Non-restrictive	Total	Mean Conc. In Vivo	Nominal Conc. In Vitro

"Honda1" uses plasma concentration, restrictive clearance, and treats the unbound invivo concentration as bioactive. For IVIVE, any input nominal concentration in vitro should be converted to cfree.invitro using armitage_eval, otherwise performance will be the same as "Honda2".

Value

A list of tissue, bioactive.free.invivo, and restrictive.clearance assumptions.

Author(s)

Greg Honda and John Wambaugh

References

Honda GS, Pearce RG, Pham LL, Setzer RW, Wetmore BA, Sipes NS, Gilbert J, Franz B, Thomas RS, Wambaugh JF (2019). “Using the concordance of in vitro and in vivo data to evaluate extrapolation assumptions.” PloS one, 14(5), e0217564.

Examples

honda.ivive(method = "Honda1", tissue = NULL)