Good afternoon -
I am curious if anyone could tell me if any of the limited sampling
design software are able to handle enterohepatic recirculation models.
Specifically, I have a model that is coded as follows:
$PK
IF(AMT.GT.0)PODO=AMT
MU_1=LOG(THETA(1))
KA1=EXP(MU_1+ETA(1))
BIO=1 ; bioavailability = 1 for tablet
MU_2=LOG(THETA(2))
MTT=EXP(MU_2+ETA(2))
MU_3=LOG(THETA(3))
N=EXP(MU_3+ETA(3))
F1=0
TVK20=THETA(4)
K20=TVK20*EXP(ETA(4))
TVV=THETA(5)
V=TVV*EXP(ETA(5))
TVK23=THETA(6)
K23=TVK23*EXP(ETA(6))
TVK32=THETA(7)
K32=TVK32*EXP(ETA(7))
TVK35=THETA(8)
K35=TVK35*EXP(ETA(8))
TVK53=THETA(9)
K53=TVK53*EXP(ETA(9))
TVK24=THETA(10)
K24=TVK24*EXP(ETA(10))
TVK41=THETA(11)
K41=TVK41*EXP(ETA(11))
TVMTIME1=THETA(12)
MTIME(1)=TVMTIME1*EXP(ETA(12))
TVDUR=THETA(13)
MTIME(2)=MTIME(1)+TVDUR*EXP(ETA(13))
S2=V
S3=V
S6=V
K12=KA1
KTR=(N+1)/MTT
LNFAC=LOG(2.5066)+(N+0.5)*LOG(N)-N
MU_4=LOG(TVK20)
MU_5=LOG(TVV)
MU_6=LOG(TVK23)
MU_7=LOG(TVK32)
MU_8=LOG(TVK35)
MU_9=LOG(TVK53)
MU_10=LOG(TVK24)
MU_11=LOG(TVK41)
MU_12=LOG(TVMTIME1)
MU_13=LOG(TVDUR)
$DES
DL=1/100000
FLAG=MPAST(1)-MPAST(2)
DADT(1)=EXP(LOG(BIO*PODO+DL)+LOG(KTR+DL)+N*LOG(KTR*T+DL)-KTR*T-LNFAC)-K1
2*A(1)+K41*A(4)*FLAG
DADT(2)=K12*A(1)-(K23+K20+K24)*A(2)+K32*A(3)
DADT(3)=K23*A(2)-(K35+K32)*A(3)+K53*A(5)
DADT(4)=K24*A(2)-K41*A(4)*FLAG
DADT(5)=K35*A(3)-K53*A(5)
Since I am using the MPAST coding in NONMEM to account for the EHR, is
there any way that I can use this type of coding (or a variation
thereof) with any of the optimal design software programs that are
available? If not, I was curious if anyone has any experience with
designing limited sampling strategies in the context of enterohepatic
recirculation and could possibly give me some advice.
Thanks in advance -
Al
Alexander Berg, Ph.D./Pharm.D.
Clinical Pharmacology Fellow
Mayo Clinic - Rochester
[email protected]
507-284-4303
Limited Sampling with Enterohepatic Recirculation
Hi Al
I presume by limited sampling design software you are referring to optimal
sampling software? There are some historical differences between how the terms
limited and optimal sampling are used.
Without specifically trying your problem, I would believe that most optimal
design software would be able to handle this type of problem. Indeed most
problems that can be coded in NONMEM can probably be run in an optimal design
software. It's really just a matter of picking your preference. For instance
the Adapt series covers single subject optimal design and programmes like PFIM,
PopED, PopDes, WinPOPT, PKStamp handle population problems (at the time of
writing this I was unable to locate PKStamp via google).
There is a population optimal design listserver:
[email protected]<mailto:[email protected]> which
specifically handles questions of this nature (you need to join up at
http://lists.otago.ac.nz/listinfo/popdesign to use it).
I am not aware of any limited sampling software.
Regards
Steve
--
Professor Stephen Duffull
Chair of Clinical Pharmacy
School of Pharmacy
University of Otago
PO Box 56 Dunedin
New Zealand
E: [email protected]<mailto:[email protected]>
P: +64 3 479 5044
F: +64 3 479 7034
W: http://pharmacy.otago.ac.nz/profiles/stephenduffull
Design software: http://www.winpopt.com
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Berg, Alexander K., Pharm.D., Ph.D.
Sent: Saturday, 7 May 2011 10:51 a.m.
To: [email protected]
Subject: [NMusers] Limited Sampling with Enterohepatic Recirculation
Good afternoon -
I am curious if anyone could tell me if any of the limited sampling design
software are able to handle enterohepatic recirculation models. Specifically,
I have a model that is coded as follows:
$PK
IF(AMT.GT.0)PODO=AMT
MU_1=LOG(THETA(1))
KA1=EXP(MU_1+ETA(1))
BIO=1 ; bioavailability = 1 for tablet
MU_2=LOG(THETA(2))
MTT=EXP(MU_2+ETA(2))
MU_3=LOG(THETA(3))
N=EXP(MU_3+ETA(3))
F1=0
TVK20=THETA(4)
K20=TVK20*EXP(ETA(4))
TVV=THETA(5)
V=TVV*EXP(ETA(5))
TVK23=THETA(6)
K23=TVK23*EXP(ETA(6))
TVK32=THETA(7)
K32=TVK32*EXP(ETA(7))
TVK35=THETA(8)
K35=TVK35*EXP(ETA(8))
TVK53=THETA(9)
K53=TVK53*EXP(ETA(9))
TVK24=THETA(10)
K24=TVK24*EXP(ETA(10))
TVK41=THETA(11)
K41=TVK41*EXP(ETA(11))
TVMTIME1=THETA(12)
MTIME(1)=TVMTIME1*EXP(ETA(12))
TVDUR=THETA(13)
MTIME(2)=MTIME(1)+TVDUR*EXP(ETA(13))
S2=V
S3=V
S6=V
K12=KA1
KTR=(N+1)/MTT
LNFAC=LOG(2.5066)+(N+0.5)*LOG(N)-N
MU_4=LOG(TVK20)
MU_5=LOG(TVV)
MU_6=LOG(TVK23)
MU_7=LOG(TVK32)
MU_8=LOG(TVK35)
MU_9=LOG(TVK53)
MU_10=LOG(TVK24)
MU_11=LOG(TVK41)
MU_12=LOG(TVMTIME1)
MU_13=LOG(TVDUR)
$DES
DL=1/100000
FLAG=MPAST(1)-MPAST(2)
DADT(1)=EXP(LOG(BIO*PODO+DL)+LOG(KTR+DL)+N*LOG(KTR*T+DL)-KTR*T-LNFAC)-K12*A(1)+K41*A(4)*FLAG
DADT(2)=K12*A(1)-(K23+K20+K24)*A(2)+K32*A(3)
DADT(3)=K23*A(2)-(K35+K32)*A(3)+K53*A(5)
DADT(4)=K24*A(2)-K41*A(4)*FLAG
DADT(5)=K35*A(3)-K53*A(5)
Since I am using the MPAST coding in NONMEM to account for the EHR, is there
any way that I can use this type of coding (or a variation thereof) with any of
the optimal design software programs that are available? If not, I was curious
if anyone has any experience with designing limited sampling strategies in the
context of enterohepatic recirculation and could possibly give me some advice.
Thanks in advance -
Al
Alexander Berg, Ph.D./Pharm.D.
Clinical Pharmacology Fellow
Mayo Clinic - Rochester
[email protected]
507-284-4303