Dear NMusers
I have collected from several studies PK data from healthy subjects, via IV and
SubCut and patients via both routes and would like to model them all together.
For all subjects, only one dose level via one administration was given. From
exploration of raw data, it is observed that there might be some difference in
bioavailability from SubCut between healthy subjects and patients. I tried the
model using ADVAN5, the parameterisation is listed below.
My questions are:
Is the model with six THETAs and ETAs an identifiable model? NOTE: NONMEM run
with this model is successful, also the estimates for CL,V2,Q and V3 are
similar to results with IV data alone.
What is a better way to explore the potential difference in PK between healthy
subjects and patients with SubCut?
Finally, I also tried to model K12 as K12=0, IF(ROUT.GT.1)
K12=EXP(THETA(5)+ETA(5)), could anyone help explain why this is wrong? NONMEM
gave the following error message:
0PRED EXIT CODE = 1
0INDIVIDUAL NO. 1 ID=0.10080000E+04 (WITHIN-INDIVIDUAL) DATA REC NO.
2
THETA=
1.10E+00 1.40E+00 5.00E-01 2.50E+00 -1.10E+00 5.00E-01
NUMERICAL DIFFICULTIES OBTAINING THE SOLUTION.
THE COEFFICIENT MATRIX IS ALGORITHMICALLY SINGULAR.
Thanks for the help.
Shuying Yang
Clinical Pharmacology Modelling and Simulation
GlaxoSmithKline
CMT = 1 for SubCut dose record, and CMT=2 for IV dose record
ROUT=1 for IV and ROUT=2 for SubCut
CL = EXP(THETA(1)+ETA(1))
V2 = EXP(THETA(2)+ETA(2))
Q = EXP(THETA(3)+ETA(3))
V3 = EXP(THETA(4)+ETA(4))
K20 = CL/V2
K23 = Q/V2
K32 = Q/V3
K12 = EXP(THETA(5)+ETA(5))
RO = EXP(THETA(6)+ETA(6))
F1=0
IF(ROUT.GT.1) F1=RO/(1+RO)
$THETA
1.0 ; CL
1.2 ; V2
0.5 ; Q
1.5 ; V3
-1.3 ; LOG(KA) /DAY
1.3 ; LOGIT(F1)
$OMEGA 0.05 ;CL
$OMEGA 0.06 ;V2
$OMEGA 0.1 ; Q
$OMEGA 0.05 ;V3
$OMEGA 0.05 ; LOG KA
$OMEGA 0.05 ; LOGIT F1
$SIGMA
0.02; PROPORTIONAL
2000; ADDITIVE
-----------------------------------------------------------
This e-mail was sent by GlaxoSmithKline Services Unlimited
(registered in England and Wales No. 1047315), which is a
member of the GlaxoSmithKline group of companies. The
registered address of GlaxoSmithKline Services Unlimited
is 980 Great West Road, Brentford, Middlesex TW8 9GS.