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#' Calculate the volume of distribution for a one compartment model.
#'
#' This function predicts partition coefficients for all tissues using
#' \code{\link{predict_partitioning_schmitt}}, then lumps them
#' into a single compartment.
#'
#' The effective volume of distribution is calculated by summing each tissues
#' volume times it's partition coefficient relative to plasma. Plasma, and the
#' paritioning into RBCs are also added to get the total volume of distribution
#' in L/KG BW. Partition coefficients are calculated using Schmitt's (2008)
#' method. When species is specified as rabbit, dog, or mouse, the function
#' uses the appropriate physiological data(volumes and flows) but substitues
#' human fraction unbound, partition coefficients, and intrinsic hepatic
#' clearance.
#'
#'
#'
#' @param chem.name Either the chemical name or the CAS number must be
#' specified when Funbound.plasma is not given in parameter list.
#' @param chem.cas Either the CAS number or the chemical name must be specified
#' when Funbound.plasma is not given in parameter list.
#'
#' @param dtxsid EPA's DSSTox Structure ID (\url{https://comptox.epa.gov/dashboard})
#' the chemical must be identified by either CAS, name, or DTXSIDs
#'
#' @param parameters Parameters from parameterize_3comp, parameterize_pbtk or
#' predict_partitioning_schmitt.
#'
#' @param default.to.human Substitutes missing animal values with human values
#' if true.
#'
#' @param species Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or
#' default "Human").
#'
#' @param suppress.messages Whether or not the output message is suppressed.
#'
#' @param adjusted.Funbound.plasma Uses adjusted Funbound.plasma when set to
#' TRUE along with parition coefficients calculated with this value.
#'
#' @param regression Whether or not to use the regressions in calculating
#' partition coefficients.
#'
#' @param minimum.Funbound.plasma Monte Carlo draws less than this value are set
#' equal to this value (default is 0.0001 -- half the lowest measured Fup in our
#' dataset).
#'
#' @return \item{Volume of distribution}{Units of L/ kg BW.}
#'
#' @author John Wambaugh and Robert Pearce
#'
#' @references Schmitt W. "General approach for the calculation of tissue to
#' plasma partition coefficients." Toxicology In Vitro, 22, 457-467 (2008).
#' Peyret, T., Poulin, P., Krishnan, K., "A unified algorithm for predicting
#' partition coefficients for PBPK modeling of drugs and environmental
#' chemicals." Toxicology and Applied Pharmacology, 249, 197-207 (2010).
#'
#' @keywords Parameter 1compartment
#'
#' @seealso \code{\link{predict_partitioning_schmitt}}
#'
#' @seealso \code{\link{tissue.data}}
#'
#' @seealso \code{\link{physiology.data}}
#'
#' @examples
#'
#' calc_vdist(chem.cas="80-05-7")
#' calc_vdist(chem.name="Bisphenol A")
#' calc_vdist(chem.name="Bisphenol A",species="Rat")
#'
#' @export calc_vdist
calc_vdist<- function(chem.cas=NULL,
chem.name=NULL,
dtxsid=NULL,
parameters=NULL,
default.to.human=FALSE,
species="Human",
suppress.messages=FALSE,
adjusted.Funbound.plasma=TRUE,
regression=TRUE,
minimum.Funbound.plasma=0.0001)
{
physiology.data <- physiology.data
Parameter <- NULL
# We need to describe the chemical to be simulated one way or another:
if (is.null(chem.cas) &
is.null(chem.name) &
is.null(dtxsid) &
is.null(parameters))
stop('Parameters, chem.name, chem.cas, or dtxsid must be specified.')
if (is.null(parameters))
{
# Look up the chemical name/CAS, depending on what was provide:
out <- get_chem_id(
chem.cas=chem.cas,
chem.name=chem.name,
dtxsid=dtxsid)
chem.cas <- out$chem.cas
chem.name <- out$chem.name
dtxsid <- out$dtxsid
schmitt.parameters <- parameterize_schmitt(chem.cas=chem.cas,
chem.name=chem.name,
dtxsid=dtxsid,
default.to.human=default.to.human,
species=species,
minimum.Funbound.plasma=minimum.Funbound.plasma)
parameters <- suppressWarnings(predict_partitioning_schmitt(
parameters=schmitt.parameters,
species=species,
regression=regression,
adjusted.Funbound.plasma=adjusted.Funbound.plasma,
minimum.Funbound.plasma=minimum.Funbound.plasma))
if (adjusted.Funbound.plasma) parameters <-
c(parameters,schmitt.parameters['Funbound.plasma'])
else parameters <-
c(parameters,Funbound.plasma=schmitt.parameters[['unadjusted.Funbound.plasma']])
}
if(any(names(parameters) %in% schmitt.specific.names) &
!all(schmitt.specific.names %in% names(parameters)))
stop("All predict_partitioning_schmitt coefficients must be included if not using pbtk or 3compartment parameters.")
else if(all(model.list[["schmitt"]]$param.names %in% names(parameters)))
schmitt.params <- T
else schmitt.params <- F
if(schmitt.params & !('funbound.plasma' %in% tolower(names(parameters))))
{
if (is.null(chem.cas) & is.null(chem.name))
stop("Specify chem.name or chem.cas with correct species if not including Funbound.plasma with predict_partitioning_schmitt coefficients.")
else if(is.null(chem.cas))
{
out <- get_chem_id(chem.cas=chem.cas,chem.name=chem.name)
chem.cas <- out$chem.cas
}
fup <- try(get_invitroPK_param("Funbound.plasma",species,chem.cas=chem.cas),silent=TRUE)
if (is(fup,"try-error") & default.to.human)
{
fup <- try(get_invitroPK_param("Funbound.plasma","Human",chem.cas=chem.cas),silent=TRUE)
warning(paste(species,"coerced to Human for protein binding data."))
}
if (is(fup,"try-error")) stop("Missing protein binding data for given species. Set default.to.human to true to substitute human value.")
if (fup == 0)
{
fup <- 0.005
warning("Fraction unbound = 0, changed to 0.005.")
}
if(adjusted.Funbound.plasma){
Flipid <- subset(physiology.data,
Parameter=='Plasma Effective Neutral Lipid Volume Fraction')[,
which(tolower(colnames(physiology.data)) == tolower(species))]
pKa_Donor <- suppressWarnings(get_physchem_param("pKa_Donor",
chem.cas=chem.cas))
pKa_Accept <- suppressWarnings(get_physchem_param("pKa_Accept",
chem.cas=chem.cas))
Pow <- 10^get_physchem_param("logP",chem.cas=chem.cas)
ion <- calc_ionization(pH=7.4,pKa_Donor=pKa_Donor,pKa_Accept=pKa_Accept)
dow <- Pow * (ion$fraction_neutral + 0.001 * ion$fraction_charged +
ion$fraction_zwitter)
fup <- 1 / ((dow) * Flipid + 1 / fup)
}
parameters <- c(parameters,Funbound.plasma=fup)
}
# Check the species argument for capitalization problems and whether or not it
# is in the table:
if (!(species %in% colnames(physiology.data)))
{
if (toupper(species) %in% toupper(colnames(physiology.data)))
{
phys.species <- colnames(physiology.data)[
toupper(colnames(physiology.data))==toupper(species)]
} else stop(paste("Physiological PK data for",species,"not found."))
} else phys.species <- species
# Load the physiological parameters for this species
this.phys.data <- physiology.data[,phys.species]
names(this.phys.data) <- physiology.data[,1]
if ("hematocrit" %in% names(parameters))
{
hematocrit <- parameters[["hematocrit"]]
} else hematocrit <- this.phys.data["Hematocrit"]
plasma.vol <- this.phys.data["Plasma Volume"]/1000 # L/kg BW
RBC.vol <- plasma.vol/(1 - hematocrit)*hematocrit
if (all(schmitt.specific.names %in% names(parameters)))
{
PC.names <- names(parameters)[regexpr("K",names(parameters))==1] #Should pass only
#partition coefficients to lump_tissues()
if (is.data.table(parameters))
{
PCs <- parameters[,PC.names,with=FALSE]
} else {
PCs <- subset(parameters,names(parameters) %in% PC.names)
}
# Get_lumped_tissues returns a list with the lumped PCs, vols, and flows:
lumped_params <- lump_tissues(
PCs,
tissuelist=NULL,
species=species,
model="1compartment")
vol.dist <- plasma.vol +
RBC.vol*lumped_params$Krbc2pu*parameters$Funbound.plasma+
lumped_params$Krest2pu*lumped_params$Vrestc*parameters$Funbound.plasma
} else {
if(!all(model.list[["schmitt"]]$param.names %in% names(parameters)) &
!all(model.list[["3comp"]]$param.names %in% names(parameters)) &
!all(model.list[["pbtk"]]$param.names %in% names(parameters)))
stop("Use parameter lists from parameterize_pbtk, parameterize_3compartment, or predict_partitioning_schmitt only.")
vol.dist <- plasma.vol +
RBC.vol*parameters[["Krbc2pu"]]*parameters$Funbound.plasma
lastchar <- function(x){substr(x, nchar(x), nchar(x))}
firstchar <- function(x){substr(x, 1,1)}
scaled.volumes <- names(parameters)[firstchar(names(parameters))=="V" &
lastchar(names(parameters))=="c"]
PCs <- names(parameters)[firstchar(names(parameters))=="K"]
comps <- intersect(substr(scaled.volumes,2,nchar(scaled.volumes)-1),
substr(PCs,2,nchar(PCs)-3))
comps <- comps[!(comps %in% c('art','ven'))]
for(this.comp in comps){
eval(parse(text=paste('vol.dist <- vol.dist + ',
parameters[[scaled.volumes[grep(this.comp,scaled.volumes)]]],
'*',
parameters[[PCs[grep(this.comp,PCs)]]],
'*',
parameters$Funbound.plasma))) # L
}
}
if (!suppress.messages)
{
if (is.null(chem.name) & is.null(chem.cas))
{
cat("Volume of distribution returned in units of L/kg BW.\n")
}
else cat(paste(toupper(substr(species,1,1)),
substr(species,2,nchar(species)),
sep=''),
"volume of distribution returned in units of L/kg BW.\n")
}
return(set_httk_precision(as.numeric(vol.dist)))
}
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