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.
lump_tissues(
Ktissue2pu.in,
parameters = NULL,
tissuelist = NULL,
species = "Human",
tissue.vols = NULL,
tissue.flows = NULL,
tissuenames = NULL,
model = "pbtk",
suppress.messages = FALSE
)Ratio of concentration of chemical in red blood cells to unbound concentration in plasma.
Ratio of concentration of chemical in rest of body tissue to unbound concentration in plasma.
Volume of the rest of the body per kg body weight, L/kg BW.
Volume of the liver per kg body weight, L/kg BW.
Fraction of cardiac output flowing to the gut and liver, i.e. out of the liver.
Fraction of cardiac output flowing to the gut.
Fraction of cardiac output flowing to the kidneys.
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.
A list of physiological parameters including flows and
volumes for tissues named in Ktissue2pu.in
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 desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").
A list of volumes for tissues in tissuelist.
A list of flows for tissues in tissuelist.
A list of tissue names in tissuenames.
Specify which model (and therefore which tissues) are being considered.
Whether or not the output message is suppressed.
John Wambaugh and Robert Pearce
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.
predict_partitioning_schmitt
tissue.data
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)
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