Parent drug with metabolites and BQL
#1
Posted 28 April 2022 - 03:06 PM
#2
Posted 29 April 2022 - 08:18 PM
I suggest that you try to have a simple model ( only parent) with BLQ before going into a full blown multiple observation with BLQs.
you can have the value of the BQL in your observation and then you tick the BQL box and map the proper information or you can a have a fixed blq
https://onlinehelp.c...rm=bql&rhsyns=
Phoenix also can deal with vpc of bql when you have bql
https://onlinehelp.c...ch=vpc&rhsyns=
#3
Posted 01 June 2022 - 07:32 PM
Thanks, Sameer, for your reply.
I am using the following PML codes for modeling a parent drug with a metabolite assuming inversible metabolite formation:
test(){
deriv(A1 = (Aa * Ka)- (Cl2 * (C - C2))- (CLPar2Met * C))
deriv(Aa = - (Aa * Ka))
deriv(A2 = (Cl2 * (C - C2)))
deriv(AMet = (CLPar2Met * C)- (CLMet * C3)- (CL3 * (C3 - C4)))
urinecpt(A0Met = (CLMet * C3))
deriv(A4 = (CL3 * (C3 - C4)))
C = A1 / V
dosepoint(Aa,tlag = Tlag)
C2 = A2 / V2
error(CEpspar = 0.1)
observe(CObsPar = C + CEpspar * sqrt(1 + C^2 * (CMultStdevpar/sigma())^2))
C3 = AMet / VMet
C4 = A4 / V4
error(CEpsmet = 0.1)
observe(CObsMet = C3 + CEpsmet * sqrt(1 + C^2 * (CMultStdevmet/sigma())^2))
stparm(V = tvV * exp(nV))
stparm(Ka = tvKa * exp(nKa))
stparm(V2 = tvV2 * exp(nV2))
stparm(Cl2 = tvCl2 * exp(nCl2))
stparm(VMet = tvVMet * exp(nVMet))
stparm(CLPar2Met = tvCLPar2Met * exp(nCLPar2Met))
stparm(CLMet = tvCLMet * exp(nCLMet))
stparm(V4 = tvV4 * exp(nV4))
stparm(CL3 = tvCL3 * exp(nCL3))
stparm(Tlag = tvTlag * exp(nTlag))
stparm(CMultStdevpar = tvCMultStdevpar)
stparm(CMultStdevmet = tvCMultStdevmet)
fixef(tvV = c(, 11904761.9, ))
fixef(tvKa = c(, 1, ))
fixef(tvV2 = c(, 22874500, ))
fixef(tvCl2 = c(, 2226500, ))
fixef(tvVMet = c(, 879700.9, ))
fixef(tvCLPar2Met = c(, 2226500, ))
fixef(tvCLMet = c(, 62000, ))
fixef(tvV4 = c(, 847500, ))
fixef(tvCL3 = c(, 62000, ))
fixef(tvTlag = c(, 0.9, ))
fixef(tvCMultStdevpar = c(, 1, ))
fixef(tvCMultStdevmet = c(, 1, ))
ranef(diag(nV, nKa, nV2, nCl2, nVMet, nCLMet, nCLPar2Met, nTlag,nCL3, nV4) = c(1, 1, 1, 1, 1, 1, 1, 1, 1 ,1))
The fit is quite acceptable based on GOF plots (attached) but I am wondering if you have any suggestion to improve it .
Thanks
Edited by Davidq8, 01 June 2022 - 07:35 PM.
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