Outline

Load data

Data Clean

pkb <- pka %>% dplyr::select(subjid, Visit, time, conc)

Color

# colored data table
color<- function(data,var,color,l){
  datatable(data, options = list(
  pageLength = l), escape=FALSE) %>% formatStyle(names(data),
                                fontSize="80%",
  background = styleColorBar(var, color),
  backgroundSize = '88% 78%',
  backgroundRepeat = 'no-repeat',
  backgroundPosition = 'left')
}
color(pkb, pkb$conc, "#ddeff6" ,11)

1 Cmax: Concentration Max

Cmax: the maximum concentration of a drug (usually measured in plasma or serum) after administration, which is a key parameter in pharmacokinetics (PK). It signifies the peak concentration reached by the drug in the bloodstream following administration.

Cmax is at patient level, one Cmax per patient.

cmax <- pkb %>%
  group_by(subjid) %>%
  summarise(Cmax = max(conc))
color(cmax, cmax$Cmax, "#ddeff6" ,11)

2 AUC: Area Under the Curve

AUC: the area under the curve (AUC) is the integral of a function and is used to calculate the total exposure to a drug after administration that represents the total exposure of a drug in the body over time. It is a key parameter in pharmacokinetics (PK) and is used to determine the bioavailability of a drug. AUC provides valuable information about the drug’s absorption, distribution, metabolism, and elimination processes.

PKNCA package is used to calculate AUC.

se <- function(n,v) { 
  df<- pkb %>% filter(subjid==n, Visit==v)
}

auc1 <- function(df){
auc<-pk.calc.aucint(conc=df$conc,time=df$time,interval=c(0,6))
}
plotc<- function(b){
lb <- paste0("AUC for Subjid " , b$subjid[1], " at ",  b$Visit[1])
ggplot(b,
       aes(x=time,
           y=conc,
           group=subjid)) +
  geom_ribbon(data=b,
              aes(ymin=0, ymax=conc),
              fill="#d7e1d0", alpha=0.6) +
  geom_line() +  theme_minimal()+
  geom_point(size=4) +
  scale_x_continuous(breaks=b$time) +
  labs(y = "Plasma Concentration ng/ML", x = "Injection Time (Hours)", title=lb)}

2.1 subjid 1

2.1.1 Day 1

b<-se("1", "D1")
b1a <- data.frame(auc1(b))
kable(b1a)
auc1.b.
305.1906 
plotc(b)

3 T1/2 half time

T1/2: the time it takes for the concentration of a drug in the bloodstream to decrease by half. It is a key parameter in pharmacokinetics (PK) and is used to determine the rate of elimination of a drug from the body. t-half is calculated by fitting the natural logarithm of concentration by time.

PKNCA package is used to calculate T1/2.

se1 <- function(n,v) { 
  df<- pk1a %>% filter(subjid==n, Visit==v)
}

th <- function(df) {
PKNCA.options(allow.tmax.in.half.life=TRUE)
thalf<-pk.calc.half.life(conc=df$conc,time=df$time)
}

th1 <- function(df,out) {
PKNCA.options(allow.tmax.in.half.life=TRUE)
thalf<-pk.calc.half.life(conc=df$conc,time=df$time)
out <- data.frame(thalf)
kable(out)
}
ploth<- function(bt){
lb <- paste0("Half time for Subjid " , bt$subjid[1], " at ",  bt$Visit[1]) 
ggplot(bt,
       aes(x=time,
           y=conc,
           group=subjid)) +
  geom_ribbon(data=bt,
              aes(ymin=0, ymax=conc),
              fill="#a3bbdb", alpha=0.6) +
  geom_line() +  theme_minimal()+
  geom_point(size=4) +
  scale_x_continuous(breaks=bt$time) +
  labs(y = "Plasma Concentration ng/ML", x = "Injection Time (Hours)", title=lb)}

3.1 subjid 1

3.1.1 Day 1

bt<-se1("1", "D1")
th1(bt, b1at)
lambda.z r.squared adj.r.squared lambda.z.time.first lambda.z.n.points clast.pred half.life span.ratio tmax tlast
0.0914 0.9717344 0.9434688 1 3 43.01866 7.583663 0.659312 1 6 
ploth(bt)

4 PKNCA for validation.

conc_obj <- PKNCAconc(b, conc~time|subjid)
data_obj <- PKNCAdata(data.conc=conc_obj,
                      intervals=data.frame(start=0,
                                           end=6,
                                           aucall=TRUE,
                                           auclast=TRUE,
                                           aucinf.pred=TRUE,
                                           aucinf.obs=TRUE))
results_obj <- pk.nca(data_obj)
## No dose information provided, calculations requiring dose will return NA.
kable(as.data.frame(results_obj))
subjid start end PPTESTCD PPORRES exclude
1 0 6 auclast 305.1905570 NA
1 0 6 aucall 305.1905570 NA
1 0 6 tmax 1.0000000 NA
1 0 6 tlast 6.0000000 NA
1 0 6 clast.obs 43.8000000 NA
1 0 6 lambda.z 0.0914000 NA
1 0 6 r.squared 0.9717344 NA
1 0 6 adj.r.squared 0.9434688 NA
1 0 6 lambda.z.time.first 1.0000000 NA
1 0 6 lambda.z.n.points 3.0000000 NA
1 0 6 clast.pred 43.0186561 NA
1 0 6 half.life 7.5836634 NA
1 0 6 span.ratio 0.6593120 NA
1 0 6 aucinf.obs 784.4025742 NA
1 0 6 aucinf.pred 775.8539579 NA

Reference:

PKNCA :

[https://cran.r-project.org/web/packages/PKNCA/vignettes/v05-auc-calculation-with-PKNCA.html]

[https://cran.r-project.org/web/packages/PKNCA/vignettes/v06-half-life-calculation.html]