route of administration
absorption
delay
distribution
elimination
output
pkmodelCode.R
ui.R
Download
library(shinydashboard)
library(mlxR)
sidebar <- dashboardSidebar(
hr(),
sidebarMenu(
menuItem("Plot", tabName = "plot", icon = icon("line-chart")),
menuItem("Codes", icon = icon("file-text-o"),
menuSubItem("pkmodelCode.R", tabName = "pkmodel", icon = icon("angle-right")),
menuSubItem("ui.R", tabName = "ui", icon = icon("angle-right")),
menuSubItem("server.R", tabName = "server", icon = icon("angle-right"))
),
menuItem("ReadMe", tabName = "readme", icon = icon("mortar-board"))
# menuItem("a", tabName = "perso", icon = icon("user"))
),
hr(),
sidebarMenu(
menuItem("Administration", tabName = "admin", icon = icon("chevron-circle-right")),
menuItem("Parameterization", icon = icon("chevron-circle-right"),
fluidRow(
column(1),
column(10,
radioButtons("parameterization","",c("rate constant" = "1","clearance" = "2"))
)) ),
menuItem("Model", icon = icon("chevron-circle-right"),
menuSubItem("Absorption", tabName = "absorption", icon = icon("angle-right")),
menuSubItem("Distribution", tabName = "distribution", icon = icon("angle-right")),
menuSubItem("Elimination", tabName = "elimination", icon = icon("angle-right"))
),
menuItem("Output", tabName = "output", icon = icon("chevron-circle-right"))
),
hr()
# conditionalPanel(condition = "input.distribution==2 | input.distribution==3" ,
# checkboxInput("cmt1", "Compartment 1 (central)", TRUE),
# checkboxInput("cmt2", "Compartment 2 (peripheral)", FALSE)
# ),
# conditionalPanel(condition = "input.distribution==3" ,
# checkboxInput("cmt3", "Compartment 3 (peripheral)", FALSE)
# )
)
body <- dashboardBody(
tabItems(
tabItem(tabName = "plot",
fluidRow(
box(width = 12, status = "primary",
# verbatimTextOutput("dynamic_value")
plotOutput("plot", height="400px")
),
tabItems(
tabItem(tabName = "admin",
box(width = 4, status = "primary", solidHeader = TRUE, title="route of administration",
radioButtons("administration", "",
c("iv bolus" = "bolus","iv infusion" = "infusion","oral" = "oral"),selected="oral")
),
box(width = 4, status = "primary",
sliderInput("tfd", "Time of first dose:", value=0, min=0, max = 20, step=1),
sliderInput("nd", "Number of doses:", value=4, min=0, max = 10, step=1)
),
box(width = 4, status = "primary",
sliderInput("ii", "Interdose interval:", value = 9, min = 0.5, max = 15, step=0.5),
sliderInput("amt", "Amount:", value = 5, min = 0, max = 20, step=1),
conditionalPanel(condition = "input.administration == 'infusion'",
sliderInput("tinf", "Infusion time:", value = 1, min = 0, max = 5, step=0.2)
)
)
),
tabItem(tabName = "absorption",
conditionalPanel(condition = "input.administration == 'oral'",
box(width = 4, status = "primary", solidHeader = TRUE, title="absorption",
radioButtons("absorption","",c("first order" = "1","zero order" = "0")),
conditionalPanel(condition = "input.absorption == '1'",
sliderInput("ka", "rate constant ka:", value = 0.8, min = 0, max = 4, step=0.1)
),
conditionalPanel(condition = "input.absorption == '0'",
sliderInput("tk0", "duration Tk0:", value = 3, min = 0, max = 10, step=0.5)
)
),
box(width = 4, status = "primary", solidHeader = TRUE, title="delay",
conditionalPanel(condition = "input.absorption == '0'",
selectInput("delay0","",c("none" = "0","lag time" = "1"))
),
conditionalPanel(condition = "input.absorption == '1'",
selectInput("delay1","",c("none" = "0","lag time" = "1","transit compartment" = "2"))
),
# conditionalPanel(condition = "input.delay1 == '1' | input.delay0 == '1' ",
conditionalPanel(condition = "(input.absorption == '1' & input.delay1 == '1') | (input.absorption == '0' & input.delay0 == '1')",
sliderInput("tlag", "lag time Tlag:", value = 1, min = 0, max = 10, step=0.5)
),
conditionalPanel(condition = "input.absorption == '1' & input.delay1 == '2'",
sliderInput("mtt", "mean transit time Mtt:", value = 1, min = 0, max = 10, step=0.5),
sliderInput("ntr", "number of compartments Ntr:", value = 2, min = 0.5, max = 10, step=0.5)
)
)
)
),
tabItem(tabName = "distribution",
# fluidRow(
box(width = 4, status = "primary", solidHeader = TRUE, title="distribution",
radioButtons("distribution","",c("1 compartment" = "1","2 compartments" = "2","3 compartments" = "3")),
sliderInput("v", "volume V:", value = 10, min = 1, max = 20, step=1)
),
box(width = 4, status = "primary",
conditionalPanel(condition = "input.distribution != '1' & input.parameterization=='1'",
sliderInput("k12", "transition rate constant k12:", value = 0.4, min = 0, max = 2, step=0.05),
sliderInput("k21", "transition rate constant k21:", value = 0.2, min = 0, max = 2, step=0.05)
),
conditionalPanel(condition = "input.distribution != '1' & input.parameterization=='2'",
sliderInput("v2", "periph. comp. volume V2:", value = 5, min = 1, max = 10, step=0.5),
sliderInput("q2", "inter comp. clearance Q2:", value = 0.5, min = 0.1, max = 2, step=0.1)
)
),
box(width = 4, status = "primary",
conditionalPanel(condition = "input.distribution == '3' & input.parameterization=='1'",
sliderInput("k13", "transition rate constant k13:", value = 0.4, min = 0, max = 2, step=0.05),
sliderInput("k31", "transition rate constant k31:", value = 0.2, min = 0, max = 2, step=0.05)
),
conditionalPanel(condition = "input.distribution == '3' & input.parameterization=='2'",
sliderInput("v3", "periph. comp. volume V3:", value = 5, min = 1, max = 10, step=0.5),
sliderInput("q3", "inter comp. clearance Q3:", value = 0.5, min = 0.1, max = 2, step=0.1)
)
)
),
tabItem(tabName = "elimination",
box(width = 4, status = "primary", solidHeader = TRUE, title="elimination",
radioButtons("elimination","",c("linear" = "1","Michaelis Menten" = "2"))
),
box(width = 4, status = "primary",
conditionalPanel(condition = "input.elimination=='1' & input.parameterization=='1'",
sliderInput("k", "elimination rate constant k:", value = 0.2, min = 0, max = 2, step=0.05)
#uiOutput('myk')
),
conditionalPanel(condition = "input.elimination == '1' & input.parameterization=='2'",
sliderInput("Cl", "Clearance Cl:", value = 1, min = 0, max = 2, step=0.05)
#uiOutput('myk')
),
conditionalPanel(condition = "input.elimination == '2'",
sliderInput("vm", "Vm:", value = 1, min = 0, max = 5, step=0.05),
sliderInput("km", "Km:", value = 1, min = 0, max = 5, step=0.05)
)
)
),
tabItem(tabName = "output",
box(width = 4, status = "primary", solidHeader = TRUE, title="output",
radioButtons("log", "", c("linear scale" = FALSE,"log scale" = TRUE))
),
box(width = 4, status = "primary",
sliderInput("range", "time range", min = -10, max = 200, value = c(-5,100), step=5),
sliderInput("ngp", "grid size", min = 10, max = 1000, value = 200, step=10),
sliderInput("lsize", "line width", min = 0, max = 2, value = 0.75, step=0.25)
)
)
)
)
),
tabItem(tabName = "pkmodel",
box( width = NULL, status = "primary", solidHeader = TRUE, title="pkmodelCode.R",
downloadButton('downloadData1', 'Download'),
br(),br(),
verbatimTextOutput("RFile")
)
),
tabItem(tabName = "ui",
box( width = NULL, status = "primary", solidHeader = TRUE, title="ui.R",
downloadButton('downloadData2', 'Download'),
br(),br(),
pre(includeText("ui.R"))
)
),
tabItem(tabName = "server",
box( width = NULL, status = "primary", solidHeader = TRUE, title="server.R",
downloadButton('downloadData3', 'Download'),
br(),br(),
pre(includeText("server.R"))
)
),
tabItem(tabName = "readme",
withMathJax(),
includeMarkdown("ReadMe.Rmd")
),
tabItem(tabName = "perso",
h4("Marc Lavielle"),
"Inria Saclay, Popix team",br(),
"April 24th, 2015"
)
)
)
dashboardPage(
dashboardHeader(title = "Build your PK model"),
sidebar,
body
)
server.R
Download
# library(mlxR)
my.dir=getwd()
source("../../initMlxR.R")
setwd(my.dir)
shinyServer(function(input, output){
l.text <- ("library(mlxR)\n")
pkmodel.text <- ("
res <- pkmodel(t,adm,p)
print(ggplot(data=res, aes(x=time, y=cc)) + geom_line(size=1) +
xlab('time (h)') + ylab('concentration (mg/L)'))
")
# output$myk <- renderUI({
# if (input$parameterization=="1"){
# sliderInput("k", "elimination rate constant k:", value = 0.2, min = 0, max = 2, step=0.05)
# }else{
# sliderInput("Cl", "Clearance Cl:", value = 1.5, min = 0, max = 3, step=0.05)
# }
# })
r <- reactive({
param.name=NULL
param.value=NULL
if (input$administration=="oral"){
if (input$absorption=="1"){
if (input$delay1=="1"){
param.name=c(param.name,'Tlag')
param.value=c(param.value,input$tlag)
}
if (input$delay1=="2"){
param.name=c(param.name,'Mtt','Ktr')
param.value=c(param.value,input$mtt,(input$ntr+1)/input$mtt)
}
param.name=c(param.name,'ka')
param.value=c(param.value,input$ka)
}else{
param.name=c(param.name,'Tk0')
param.value=c(param.value,input$tk0)
if (input$delay0=="1"){
param.name=c(param.name,'Tlag')
param.value=c(param.value,input$tlag)
}
}
}
param.name=c(param.name,'V')
param.value=c(param.value,input$v)
if (input$distribution!="1"){
if (input$parameterization=="1"){
param.name=c(param.name,'k12','k21')
param.value=c(param.value,input$k12,input$k21)
}else{
param.name=c(param.name,'Q2','V2')
param.value=c(param.value,input$q2,input$v2)
}
}
if (input$distribution=="3"){
if (input$parameterization=="1"){
param.name=c(param.name,'k13','k31')
param.value=c(param.value,input$k13,input$k31)
}else{
param.name=c(param.name,'Q3','V3')
param.value=c(param.value,input$q3,input$v3)
}
}
if (input$elimination=="1"){
if (input$parameterization=="1"){
param.name=c(param.name,'k')
param.value=c(param.value,input$k)
}else{
param.name=c(param.name,'Cl')
param.value=c(param.value,input$Cl)
}
}else{
param.name=c(param.name,'Vm','Km')
param.value=c(param.value,input$vm,input$km)
}
p=list(name=param.name,value=param.value)
t.value=seq(input$range[1],input$range[2],length.out=input$ngp)
t1=input$tfd
t2=input$ii*(input$nd-1)+t1
if (t2>=t1){
t.dose=seq(t1,t2,by=input$ii)
adm <- list(time=t.dose, amount=input$amt)
}else{
adm <- list(time=t1, amount=0)
}
if (input$administration == 'infusion'){
adm$rate <- input$amt/input$tinf
}
#----------------------------------------------------
res <- pkmodel(time=t.value,treatment=adm,parameter=p)
#----------------------------------------------------
a.text <- 'adm <- list('
if (input$nd==0){
a.text <- 'adm <- list(amount=0, time=0'
} else if(input$nd==1){
a.text <- paste0('adm <- list(amount=',input$amt,', time=',input$tfd)
} else{
t1=input$tfd
t2=input$ii*(input$nd-1)+t1
a.text <- paste0('adm <- list(amount=',input$amt,
', time=seq(',t1,', ',t2,', by=',input$ii,')')
}
if (input$administration == 'infusion'){
a.text <- paste0(a.text,', tinf=',input$tinf,')')
}else{
a.text <- paste0(a.text,')')
}
K <- length(param.value)
p.text <- 'p <- c('
for (k in (1:(K-1))){
p.text <- paste0(p.text,param.name[k],'=',param.value[k],', ')
}
p.text <- paste0(p.text,param.name[K],'=',param.value[K],')')
t.text <- paste0('t <- seq(',input$range[1],', ',input$range[2],
', length=',length.out=input$ngp,')')
pkmodel.text <- paste0(l.text,a.text,'\n',p.text,'\n',t.text,'\n',pkmodel.text)
out <- list(res,pkmodel.text)
return(out)
})
output$plot <- renderPlot({
pl=ggplotmlx(data=r()[[1]], aes(x=time, y=cc)) + geom_line(size=input$lsize)
if (input$log==TRUE)
pl=pl + scale_y_log10()
print(pl)
})
output$table <- renderTable({ r()[[1]] })
output$RFile <- renderText(r()[[2]])
output$downloadData1 <- downloadHandler(
filename = "pkmodelCode.R",
content = function(file) {
write(r()[[2]], file)
}
)
output$downloadData2 <- downloadHandler(
filename = "ui.R",
content = function(file) {
con = file("ui.R", open = "r")
lines = readLines(con)
close(con)
write(lines, file)
}
)
output$downloadData3 <- downloadHandler(
filename = "server.R",
content = function(file) {
con = file("server.R", open = "r")
lines = readLines(con)
close(con)
write(lines, file)
}
)
# output$dynamic_value <- renderPrint({
# str(input$k)
# })
})
Build your PK model
Marc Lavielle
April 24th, 2015
Select the administration route and the dosage regimen in the menu Administration:
- iv bolus, iv infusion, or oral administration,
- time of first dose,
- number of doses,
- interdose interval,
- amount.
- infusion time (only for infusion),
Define the PK model in the menu Model:
- Define the absorption process for oral administration in the submenu Absorption:
- zero-order or first-order absorption process with the associated paramameters (duration of absorption \(Tk0\) or absorption rate constant \(ka\))
- lag time \(Tlag\)
- transit compartment model with mean transit time \(Mtt\) and number of transit compartments \(Ntr\) (only for first-order absorption)
- Define the distribution process in the submenu Distribution:
- 1, 2 or 3 compartments
- volume of distribution \(V\)
- transfer rates constants \(k_{12}\) and \(k_{21}\) between compartments 1 and 2
- transfer rates constants \(k_{13}\) and \(k_{31}\) between compartments 1 and 3
- Define the elimination process in the submenu Elimination:
- linear or Michaelis Menten elimination process
- elimination rate constant \(k\), or
- Michaelis Menten parameters \(V_m\) and \(K_m\).
Define the output in the menu Output:
- select the time range where the predicted concentration is computed,
- select the number of time points of the grid where the predicted concentration is computed,
- choose between linear and semi-log scale.
Marc Lavielle
Inria Saclay, Popix teamApril 24th, 2015