Re: Antwort: Transit compartment model with multiple dose data
Dear Fabrice,
You need to add a small value to each log term in your
differential equation which may take value of zero.
Additionally, you need to add dummy lines in your data set prior
to each dosing event with EVID==2. This will help to update the
system correctly with the amounts administered.
Good luck!
Rada
On 4/13/2011 8:26 AM, Sven Mensing wrote:
Dear Fabrice,
please try
TALD=T-TDOS
IF(TALD.EQ.0) TALD = 0.0001
this might help as NONMEM cannot
compute the log of zero...
Regards
Sven Mensing
Sven Mensing, PhD
Group Leader,
Pharmacometrician
Pharmacometrics III, GGDP3
Abbott GmbH
& Co. KG
Knollstraße 50
67061 Ludwigshafen
Germany
phone: +49 (0)621 589 1535
fax: +49 (0)621 589 1925
[email protected]
---13.04.2011 08:52:02---Dear NMusers, I am
trying to implement the transit compartments absorption model
as
Von:
< [email protected] >
An:
< [email protected] >
Datum:
13.04.2011 08:52
Betreff:
[NMusers] Transit compartment model with
multiple dose data
Gesendet von:
[email protected]
Dear NMusers,
I am trying to implement the transit compartments absorption
model as
described by Savic et al. (1).
As my dataset includes some multiple dosing data, I have recoded
the actual
time as time after last dose (see code below), as suggested by
Wilkins et
al. (2)
However, I always got the following error message for the first
observation
record:
0PROGRAM TERMINATED BY OBJ
ERROR IN OBJ2 WITH INDIVIDUAL 1 ID=
1.01010000000000E+04
CONDITIONAL CONTRIBUTION OR IT'S DERIVATIVE IS INFINITE
MESSAGE ISSUED FROM ESTIMATION STEP
AT INITIAL OBJ. FUNCTION EVALUATION
I have tried to play with the initial estimates, but always with
the same
outcome.
The relevant part of the code is given here below.
Thanks in advance for any suggestion!
Fabrice
Fabrice Nollevaux,
Pharmacometrician
Arlenda SA
www.arlenda.com
(1) Savic et al. J Pharmacokinet Pharmacodyn (2007) 34:711-726
(2) Wilkins et al. Antimicrob Agents Chemother (2008)
52(6):2138-2148
...
$SUBROUTINES ADVAN6 TOL=3
$MODEL NCOMP=3
COMP(DEPOT, DEFDOSE) ; absorption compartment
COMP(CENTRAL,DEFOBS) ; central compartment
COMP(PERIPH) ; peripheral compartment
$PK
KA = THETA(1)*EXP(ETA(1))
CL = THETA(2)*EXP(ETA(2))
V2 = THETA(3)*EXP(ETA(3))
Q = THETA(4)*EXP(ETA(4))
V3 = THETA(5)*EXP(ETA(5))
KTR = THETA(8)
N = THETA(9)
S2 = V2/1000
K = CL/V2
K23 = Q/V2
K32 = Q/V3
LNFAC = LOG(2.5066)+(N+0.5)*LOG(N)-N
IF (AMT.GT.0) TDOS=TIME
$DES
TALD=T-TDOS ; Time after last dose
DADT(1) =
EXP(LOG(DOSE)+LOG(KTR)+N*LOG(KTR*TALD)-KTR*TALD-LNFAC)-KA*A(1)
DADT(2) = KA*A(1)-K*A(2)-K23*A(2)+K32*A(3)
DADT(3) = K23*A(2)-K32*A(3)
$ERROR
IPRED=F
IF (F.GT.0) THEN
W=(F*F*THETA(6)**2+THETA(7)**2)**0.5
ELSE
W=1
ENDIF
Y=F+W*EPS(1)
IRES=DV-IPRED
IWRES=IRES/W
...
Sitz der Gesellschaft: Wiesbaden,
Amtsgericht Wiesbaden HRA 4888
Persönlich haftende Gesellschafterin:
Abbott Management GmbH
Sitz der Gesellschaft: Wiesbaden,
Amtsgericht Wiesbaden HRB 12889
Geschäftsführer: Dr. Friedrich Richter,
Alexander Würfel, Luc Ruysen, Matthias
Däschner
Vorsitzender des Aufsichtsrates: Brian
Blaser
Disclaimer
Der Inhalt dieser Nachricht ist
vertraulich, kann gesetzlichen Bestimmungen
unterliegen, kann vertrauliche Informationen
beinhalten und ist nur für den direkten
Empfänger bestimmt. Sie ist Eigentum von Abbott
Laboratories bzw. der betreffenden
Niederlassung. Nicht authorisierte Benutzung,
unbefugte Weitergabe sowie Kopieren jeglicher
Bestandteile dieser Information ist streng
verboten und kann als rechtswidrige Handlung
eingestuft werden. Sollten Sie diese Nachricht
fälschlicherweise erhalten haben, informieren
Sie bitte Abbott Laboratories umgehend, indem
Sie die Email zurückschicken und diese dann
zusammen mit allen zugehörigen Kopien oder
Dateianhängen zerstören .
The information contained
in this communication is
confidential, may be subject to
legal privileges, may constitute
inside information, and is intended
only for the use of the addressee.
It is the property of Abbott
Laboratories or its relevant
affiliate. Unauthorized use,
disclosure or copying of this
communication or any part thereof is
strictly prohibited and may be
unlawful. If you have received this
communication in error, please
notify Abbott Laboratories
immediately by return e-mail and
destroy this communication and all
copies thereof, including all
attachments .
--
Rada Savic, PhD
S-009 Stanford Medical Center
Stanford, CA 94305-5130
Tel: 650.725.8020
Email: [email protected]