Date: Mon, 9 Jul 2007 06:58:34 -0700
Public StationerySince the concentration measured is in ng/ml (ug/L) you =
have to make correction as follows:
S2=V/10000 ; S2 because you are using one compartment with =
absorption (S2 - Scale for central compartment)
- Krishna R. Devarakonda
----- Original Message -----
From: Tausif Ahmed
To: nmusers_at_globomaxnm.com
Sent: Monday, July 09, 2007 4:26 AM
Subject: [NMusers] Query on model development
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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