lump_tissues: Lump tissue parameters into model compartments

In httk: High-Throughput Toxicokinetics

Lump tissue parameters into model compartments

Description

This function takes the tissue:plasma partition coefficients from predict_partitioning_schmitt along with the tissue-specific volumes and flows and aggregates (or "lumps") them according to the needed scheme of toxicokinetic model tissue comparments.

predict_partitioning_schmitt makes tissue-specific predictions drawing from those tissues described in tissue.data. Since different physiologically-based toxicokinetic (PBTK) models use diffeent schemes for rganizing the tissues of the body into differing compartments (for example, "rapidly perfused tissues"), this function lumps tissues into compartments as specified by the argument 'tissuelist'. Aggregate flows, volumes, and partition coefficients are provided for the lumped tissue compartments. Flows and volumes are summed while partition coefficients is calculated using averaging weighted by species-specific tissue volumes.

The name of each entry in 'tissuelist' is its own compartment. The modelinfo_MODEL.R file corresponding to the model specified by argument 'model' includes both a 'tissuelist' describing to the model's compartmentallumping schme as well as a vector of 'tissuenames' specifying all tissues to be lumped into those compartments.

Alternatively the 'tissuelist' and 'tissuenames' can also be manually specified for alternate lumping schemes not necessarily related to a pre-made httk model. For example, tissuelist<-list(Rapid=c("Brain","Kidney")).

The tissues contained in 'tissuenames' that are unused in 'tissuelist' are aggregated into a single compartment termed "rest".

NOTE: The partition coefficients of lumped compartments vary according to individual and species differences since the volumes of the consitutent tissues may vary.

Usage

lump_tissues(
  Ktissue2pu.in,
  parameters = NULL,
  tissuelist = NULL,
  species = "Human",
  tissue.vols = NULL,
  tissue.flows = NULL,
  tissuenames = NULL,
  model = "pbtk",
  suppress.messages = FALSE
)

Arguments

Ktissue2pu.in	List of partition coefficients from predict_partitioning_schmitt. The tissues named in this list are lumped into the compartments specified by tissuelist unless they are not present the specified model's associated alltissues.
parameters	A list of physiological parameters including flows and volumes for tissues named in Ktissue2pu.in
tissuelist	Manually specifies compartment names and tissues, which override the standard compartment names and tissues that are usually specified in a model's associated modelinfo file. Remaining tissues in the model's associated alltissues listing are lumped in the rest of the body.
species	Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").
tissue.vols	A list of volumes for tissues in tissuelist.
tissue.flows	A list of flows for tissues in tissuelist.
tissuenames	A list of tissue names in tissuenames.
model	Specify which model (and therefore which tissues) are being considered.
suppress.messages	Whether or not the output message is suppressed.

Value

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.
Vrestc	Volume of the rest of the body per kg body weight, L/kg BW.
Vliverc	Volume of the liver per kg body weight, L/kg BW.
Qtotal.liverf	Fraction of cardiac output flowing to the gut and liver, i.e. out of the liver.
Qgutf	Fraction of cardiac output flowing to the gut.
Qkidneyf	Fraction of cardiac output flowing to the kidneys.

Author(s)

John Wambaugh and Robert Pearce

References

Pearce, Robert G., et al. "Evaluation and calibration of high-throughput predictions of chemical distribution to tissues." Journal of pharmacokinetics and pharmacodynamics 44.6 (2017): 549-565.

See Also

predict_partitioning_schmitt

tissue.data

Examples

 pcs <- predict_partitioning_schmitt(chem.name='bisphenola')
 tissuelist <- list(
   liver=c("liver"),
   rapid=c("lung","kidney","muscle","brain"),
   fat=c("adipose"),
   slow=c('bone'))
 lump_tissues(pcs,tissuelist=tissuelist)

httk documentation built on Sept. 11, 2024, 9:32 p.m.