Antwort: Transit compartment model with multiple dose data

2 messages 2 people Latest: Apr 13, 2011

Antwort: Transit compartment model with multiple dose data

From: Sven Mensing Date: April 13, 2011 technical
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 Abbott GmbH & Co. KG phone: +49 (0)621 589 Group Leader, Knollstraße 50 1535 Pharmacometrician 67061 Ludwigshafen fax: +49 (0)621 589 Pharmacometrics III, GGDP3 Germany 1925 [email protected] |------------> | 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 ... <<inline: 08466182.gif>> <<inline: ecblank.gif>> <<inline: graycol.gif>> <<inline: GS_TAD_2011-rot.gif>>

Re: Antwort: Transit compartment model with multiple dose data

From: Rada Savic Date: April 13, 2011 technical
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]