From: "Kazimierz H.Kozlowski" khkoz@czd.waw.pl Subject: [NMusers] Combined exponential + differential equations in $DES for post-SS concentrations Date: Wed, June 16, 2004 2:53 pm Dear NONMEM users, I have some problem in post-infusion exponential equations and $DES. It is single subject, steady-state R1 defined in $PK and lasting at TIME=0, 2-compartment model. In the case of post-steady-state infusion stoping, first distribution phase could be much shallowed in comparison to single i.v. dose. When using combined exponential and differential equation I would like to compare this 2 method as well as accelerete computation time in the next population PK/PD analysis. Has any person has experienced with such problem? #1. Concerning central compartment I obtained identical values for A(1) computed by $DES and exponential equation computed by $ERROR, however, only similar values when computed by exponential equation computed by $DES. #2. Concerning peripherial compartment they were not acceptable differences (errous equation?) between A(2) from $DES and exponential equations. #3. It is possible resolve 2-compartment model in the case shallowed ALPHA phase when data are from post-infusion only? sincerely Kazimierz H. Kozlowski Laboratory of Pharmacokinetics The Children's Memorial Health Institute 04-736 Warsaw, Poland E-mail: khkoz@czd.waw.pl $PK . . IF (EVID.EQ.1) THEN . . PR1=RR*....... ENDIF K21=ALPHA*BETA/K10 K12=ALPHA+BETA-K21-K10 CC1A=(K21-ALPHA)/(BETA-ALPHA) ;C1' (E1=K21) CC1B=(K21-BETA)/(ALPHA-BETA) ;C2' CC2A=(K12+K10-ALPHA)/(BETA-ALPHA) ;T1' (E2=K12+K10) CC2B=(K12+K10-BETA)/(ALPHA-BETA) ;T2' AUCC=CC1A/ALPHA+CC1B/BETA ; FC1=(CC1A/ALPHA)/AUCC ;f1 for Cp equation (exponential) FC2=(CC1B/BETA)/AUCC ;f2 for Cp equation AUCT=CC2A/ALPHA+CC2B/BETA ; FT1=(CC2A/ALPHA)/AUCT ;f1 for Ct equation (also 2-exponential) FT2=(CC2B/BETA)/AUCT ;f2 for Ct equation R1=PR1* ..... ; R1 computed using RR from $DATA IF (TIME.GT.0) R1=0 $DES C1=PR1*FC1*EXP(-ALPHA*T)+PR1*FC2*EXP(-BETA*T) ; post-SS infusion end Cp (correct) C2=PR1*FT1*EXP(-ALPHA*T)+PR1*FT2*EXP(-BETA*T) ; post- SS infusion end Ct (errous?) DADT(1)=K12*(A(2)-A(1))-K10*A(1) ; Cp DADT(2)=K21*(A(1)-A(2)) ; Ct DADT(3)=............ ; Ce effect compartment model $ERROR A1=A(1) ; S1=1 A2=A(2) A3=A(3) CPP1=PR1*FC1*EXP(-ALPHA*TIME)+PR1*FC2*EXP(-BETA*TIME) CPP2=PR1*FT1*EXP(-ALPHA*TIME)+PR1*FT2*EXP(-BETA*TIME) . . _______________________________________________________