Re: [NMusers] Query on model development

Use S2=V/1000 instead of S1=V/1000
Leonid

Tausif Ahmed wrote:
>
> Dear All,
>
> I am new to the field of POP-PK.
> We are developing a POP-PK model for our in-house drug. The conc. are in
> ng/mL and dose is in mg.
> The drug is administered *orally* and follows *1-compartment* model. It
> has a short half-life of 2-3 h.
> We have developed the basic model using rich data from serial sampling
> of healthy subjects.
>
>
> -We have determined the Bayesian estimates of CL and V. But I think, we
> are overestimating these values. If we determine CL , using
> non-compartmental analysis (rich data )we are getting lower estimates
> (800 L/h), while using NONMEM (using same rich data), we are getting
> quite high estimates (mean for 25 mg- 4000 L/hr).
>
> Kindly give your inputs on further modifying this model to get an
> irreducible model and also validating the model.
>
> Thanking you in anticipation.
>
>
> Thanks and regards
> Tausif Ahmed, Ph.D.
> Senior Research Scientist
> Metabolism and Pharmacokinetics Department,
> Ranbaxy Research Lab., India
>
>
> Model:
>
>
> PROB Oral RSd-RMD-PK01-healthy study
> $DATA RSD_PK01ctdata.csv IGNORE=C
> $INPUT ID TIME CONC=DV DOSE AMT AGE WT MDV
> $SUBROUTINES ADVAN2 TRANS2; One Compartment Linear Model
> $PK
> TVCL=THETA(1) ; mean clearance
> CL=TVCL*EXP(ETA(1))
> TVV=THETA(2) ; mean central volume
> V=TVV*EXP(ETA(2))
> K=CL/V ;reparameterization required
> S1=V/1000
> KA=THETA(3)
>
> $THETA (0, 100) ; clearance estimate (L\hr)
> (0, 100) ; volume estimate (L)
> (0, 1.5) ; Absorption rate constant
>
> $OMEGA .16 .16 ; forty percent cv
>
> $SIGMA .16 ; forty percent cv
>
> $ERROR
> IPRED=F
> Y=F+ERR(1)
>
> $ESTIMATION METHOD=0 MAXEVAL=9999 PRINT=5 POSTHOC SIGDIGITS=4
>
> $COVARIANCE
>
> $TABLE ID TIME DV DOSE CL V ETA1 ETA2 AMT AGE WT MDV
>
> NOPRINT ONEHEADER FILE=CS1_oralRSDRMDPK01.PAR
>
> $SCAT CONC VS TIME
>
>
> *OUTPUT*
> **
> MINIMUM VALUE OF OBJECTIVE FUNCTION
>
>
> ************************************************** 6971.242
> **************************************************
>
> ************************************************************************************************************************
> ********************
> ******************** FINAL
> PARAMETER ESTIMATE ************************************************************************************************************************
>
>
>
> THETA - VECTOR OF FIXED EFFECTS PARAMETERS *********
>
>
> TH 1 TH 2 TH 3
>
> 4.97E+03 8.02E+03 1.70E-01
>
>
>
> OMEGA - COV MATRIX FOR RANDOM EFFECTS - ETAS ********
>
>
> ETA1 ETA2
>
> ETA1
> + 2.57E+00
>
> ETA2
> + 0.00E+00 1.14E+00
>
>
>
> SIGMA - COV MATRIX FOR RANDOM EFFECTS - EPSILONS ****
>
>
> EPS1
>
> EPS1
> + 4.72E+02
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Received on Mon Jul 09 2007 - 08:27:53 EDT