bsv and zero order absorbtion

[Dinko Rekic]

Dear all, 

What would be the preferred way of adding BSV on the rate of zero order absorption?

I understand that I can simulate different rates from the OMEGA estimate and input the rate as a variable in the dataset. But is there a better way? And what if I have off-diagonal elements in the OMEGA block?

Example code below without BSV on rate.  

.

code <- '

$PARAM TVCL = 1.23, TVV = 35.7, TVKA = 1.3

F1 = 0.82, ALAG = 1.21

WT = 70, SEX = 0

$MAIN

double CL = TVCL*pow(WT/70,0.75)*exp(ECL);

double V  = TVV*(WT/70)*exp(EV);

double KA = TVKA*exp(EKA);

if(SEX==1) V = V*0.8;

F_GUT = F1;

ALAG_GUT = ALAG;

$PKMODEL cmt="GUT CENT", depot=TRUE

$OMEGA @labels ECL EV EKA

0.015 0.2 0.5

$SIGMA @labels PROP ADD

0.03 230

$TABLE

capture IPRED = CENT/(V/1000);

capture DV = IPRED*(1+PROP)+ADD;

while(DV < 0) {

  simeps();

  DV = IPRED*(1+PROP)+ADD;

}

$CAPTURE WT CL 

'

mod <- mcode_cache("demo", code)

DUR=1.7

data <- expand.ev(ID=1:10, amt=80, rate=80/DUR, cmt="GUT", ii=24, addl=0)

out <- 

  mod %>% 

  data_set(data) %>%

  mrgsim(delta=1, end=24)

plot(out)

[Kyle Baron]

Hi Dinko - 

See the code below.  I followed your example of parameterizing this with from DUR.  In that case, set

rate to -2 in the data set and set the D_GUT variable to the duration that you want. 

If you did want to do this in terms of "rate", set rate to -1 in the data set and model R_GUT in $MAIN.

Kyle

code <- '

$PARAM TVCL = 1.23, TVV = 35.7, TVKA = 1.3

F1 = 0.82, ALAG = 1.21

WT = 70, SEX = 0, TVDUR = 1.7

$MAIN

double CL = TVCL*pow(WT/70,0.75)*exp(ECL);

double V  = TVV*(WT/70)*exp(EV);

double KA = TVKA*exp(EKA);

if(SEX==1) V = V*0.8;

F_GUT = F1;

ALAG_GUT = ALAG;

D_GUT = TVDUR * exp(EDUR);

$PKMODEL cmt="GUT CENT", depot=TRUE

$OMEGA @labels ECL EV EKA

0.015 0.2 0.5

$OMEGA @labels EDUR

0.3

$SIGMA @labels PROP ADD

0.03 230

$TABLE

capture IPRED = CENT/(V/1000);

capture DV = IPRED*(1+PROP)+ADD;

while(DV < 0) {

  simeps();

  DV = IPRED*(1+PROP)+ADD;

}

$CAPTURE WT CL 

'

mod <- mcode_cache("demo_dur", code)

DUR=1.7

data <- expand.ev(ID=1:10, amt=80, rate=-2, cmt="GUT", ii=24, addl=0)

out <- 

  mod %>% 

  data_set(data) %>%

  mrgsim(delta=0.05, end=24)

plot(out, GUT ~., xlim = c(0,12))

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Kyle Baron, PharmD, PhD

Senior Scientist
Metrum Research Group