# PharmPK Discussion - WNL user defined model - conc below zero

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• On 30 Nov 2004 at 14:45:22, =?ISO-8859-1?Q? "Cornelia_Burger" ?= (cbuerger.-a-.zedat.fu-berlin.de) sent the message
`Dear all,I am trying to write a user defined model with multiple iv infusions(WinNonlin (V4.0), please see example below).The dosing regimen contains 2 doses of 600 mg at 0 and 12 hours and aduration of infusion of 0.5 hr.Problem No. 1:Simulating the data for 2 doses with first dose of 0mg (no change inNCON) and second dose 600 mg results in concentrations below zeroduring the first 12 hours.Problem No. 2:Simulating the data for 1 dose at 12 hours (change in NCON) results ineven lower concentrations during the first 12 hours than with problemNo. 1.In my opinion, no matter which of the two approaches is used, when theinput at t=0 is zero there should be no change in the concentration andit should never fall below zero. Has anyone ever observed the samephenomena? What could be a possible explanation? Any help would behighly appreciated!Best regards,ConnyMODELCOMM    NPARM 2    NCON 7    PNAMES 'V', 'K10'    NFUNC 1    NDER 1ENDTEMP    ndose = CON(1)    INPUT = 0    T=XENDSTART    Z(1) = 0ENDDIFF    j=0    DO i=1 TO ndose       j=j+3       IF T LE CON(j) THEN goto red       ENDIF    NEXT    red:    ndose = i-1    j=0    DO i=1 TO ndose       j=j+3       Dose = CON(j-1)       TI = CON(j+1)       T = X - CON(j)       IF T GE TI THEN INPUT = 0          ELSE INPUT = Dose/TI       ENDIF       DZ(1) = (INPUT - K10*Z(1))    NEXTENDFUNCTION 1    F = Z(1)/VENDEOM`
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• On 1 Dec 2004 at 09:33:45, David Czock (david.czock.aaa.medizin.uni-ulm.de) sent the message
`The following message was posted to: PharmPKDear Conny,I assume that CON(1) is the number of doses,CON(2) is the dose, CON(3) is the begin of infusion, CON(4) is theduration of infusion, CON(5) is the next dose, ...try the following:1. delete "INPUT=0" from the TEMP section2. replace the DIFF section byj=0INPUT=0do i=1 to ndose   j=j+3   Dose=CON(j-1)   TI=CON(j+1)   IF T GT CON(j) AND T LE (CON(j)+TI) THEN     INPUT=Dose/TI   ENDIFNEXTDZ(1)=INPUT - k10*Z(1)Best wishesDavid`
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• On 1 Dec 2004 at 17:30:34, =22Cornelia_Burger=22 (cbuerger.-at-.zedat.fu-berlin.de) sent the message
`The following message was posted to: PharmPKDear David,thank you very much for your suggestion.Unfortunately although the values were closer to zero the problempersisted.But changing the function block into F=MAX(0,Z(1))/V solved the problem:).Thank you again for your help.Best regardsConny`
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