Closed AprilCCC closed 2 years ago
mattfidler
commented
2 years ago With nlmixr you cannot simulate from the un-fitted model. The upcoming nlmixr2 allows you to simulate.
However, regardless of the method you use, you need to specify residual error with the ~ syntax. This would be something like R ~ prop(e1.sd)+add(e2.sd). You also do not have to specify IPRED, IRES, IWRES in the nlmixr estimation. They are added automatically by nlmixr/nlmixr2
AprilCCC
commented
2 years ago Hi Matthew, thanks for the suggesion. I still have several questions regarding reproduce model from NONMEM code, Can you help me to check with this? Really appreciate it.
TVCLS = THETA(1)*(WT/70)*THETA(7) CLS = TVCLS EXP(ETA(1)) $THETA 0.607 FIX ; 7WT on CL
Is it correct way to write in the nlmirx? cl <- exp(lcl + eta.cl + log(WT/70) * WTcl)$DES
C1 = A(1)/VC
C2 = A(2)/VP
DADT(1) = -VMAXC1/(KM+C1)-(CLSC1)-(CLPC1)+(CLPC2)
DADT(2) = (CLPC1)-(CLPC2)Is it correct way to write in the nlmixr as below?
c1 = center / vc
c2 = periph / vp
d/dt(center) = -VM * c1/(KM+c1) - (cl *c1) -(Q * c1) + (Q * c2)
d/dt(periph) = (Q * c1) - (Q * c2)
Hi nlmixr team,
I just tried to reproduce a NONMEM popPK dose simulation from observed real data with nlmixr, and when I tried to simulate it, occurred 2 errors, and under the same dose, however, the NCA result from nlmixr model-simulated data was far from the original observed data NCA result. Can anyone help me to check what is wrong with the nlmixr model? The observed real data is in the attachment. Many thanks! observed data.xlsx
Error in .nlmixrUIModel(fun, ini, bigmodel) : There must be at least one prediction in the model({}) block. Use
~for predictions Error in configsaem(model = model, data = dat, inits = inits, mcmc = .mcmc, : covariate(s) not found: A1, A2, q, centr, VcThe NONMEN model code showed below: $SUBROUTINE ADVAN6 TOL=3 $MODEL NCOMP=2 COMP=(CENTRAL,DEFOBS,DEFDOSE) COMP=(PER) $PK
TVCLS = THETA(1)*(WT/70)*THETA(7) CLS = TVCLS EXP(ETA(1))
TVVC = THETA(2)*(WT/70)*THETA(8) VC = TVVC EXP(ETA(2))
TVCLP = THETA(3)*(WT/70)*THETA(7) CLP = TVCLP EXP(ETA(3))
TVVP = THETA(4)*(WT/70)*THETA(8) VP = TVVP EXP(ETA(4))
TVVMAX = THETA(5) VMAX = TVVMAX* EXP(ETA(5))
TVKM = THETA(6) KM = TVKM* EXP(ETA(6))
;S2=V2
$DES
C1 = A(1)/VC C2 = A(2)/VP
DADT(1) = -VMAXC1/(KM+C1)-(CLSC1)-(CLPC1)+(CLPC2) DADT(2) = (CLPC1)-(CLPC2)
$ERROR
R=A(1)/VC IPRED = R IRES = DV-IPRED IWRES = IRES/DV Y = R*(1+EPS(1))+EPS(2)
$THETA 0.0223 FIX ; 1CLS,L/h 3.26 FIX ; 2VC,L 0.0433 FIX ; 3CLP,L/h 2.72 FIX ; 4VP,L 295.4 FIX ; 5VMAX,ug/h 115 FIX ; 6KM,ng/ml 0.607 FIX ; 7WT on CL 0.371 FIX ; 8WT on V ;0 FIX ;WT on VMAX $OMEGA 0.093 FIX ; ETA_CLS 0 FIX ; ETA_VC 0 FIX ; ETA_CLP 0.87 FIX ; ETA_VP 0.161 FIX ; ETA_VAMX 0 FIX ; ETA_KM $SIGMA 0.284 FIX ; EPS(1) 14.4 FIX ; EPS(2) ng/ml $SIMULATION (889216570) ONLYSIM SUBPROBLEM=10
The nlmixr model code I created showed below: cmt2sad5 <- function(){ ini({ lv <- 3.26 lcl <- 0.0223 lQ <- 0.0433 # Q inter-compartmental CL (Q) lvp <- 2.72 # Vp peripheral volume (Vp) lVM <- 295.4 lKM <- 115 WTcl <- 0.607 WTv <-0.371 wt.est <- 0.0 eta.v ~ 0 eta.cl ~ 0.093 eta.Q ~ 0 eta.vp ~ 0.87 eta.VM ~ 0.161 eta.KM ~ 0 EPS1 ~ 0.284 EPS2 ~ 14.1 }) model({ cl <- exp(lcl + eta.cl + wt.est (WTcl/70)) vc <- exp(lv + eta.v + wt.est (WTv/70)) Q <- exp(lQ + eta.Q + wt.est (WTcl/70)) vp <- exp(lvp + eta.vp + wt.est (WTv/70)) VM <- exp(lVM + eta.VM) KM <- exp(lKM + eta.KM) c1 = A1 / vc c2 = A2 / vp d/dt(center) = -VM c1/(KM+c1) - (cl c1) -(q c1) + (q c2) d/dt(periph) = (q c1) + (q c2)
linCmt() ~ lnorm(logn.sd)
}) } cmt2msad5 <- nlmixr(cmt2sad5)
print(cmt2msad5)
cmt2fitsad5.logn <- nlmixr(cmt2msad5, sad5, "saem", control=list(print=0), table=tableControl(cwres=TRUE, npde=TRUE)) plot(augPred(cmt2fitsad5.logn))
simulation with same dose, 5mg/kg in human with 61.5kg weight in avarage
ev <- eventTable(amount.units="mg", time.units="h") %>% et(amt=5 61.5 1000) %>% et(seq(0, 504, by=1)) %>% et(id=1:60)
sim1 <- simulate(cmt2fitsad5.logn, events=ev)