Re: Translate ALAG1 and D1 in ADVAN2 to differential equations

Xiao Hu, Part 1) NONMEM handles the input of all doses automatically via the dataset structure. Therefore, generally there is no need to initialize compartments or to code infusion rates in the $DES block. An exception to this rule is when you are dosing or modeling endogenous substances. Assuming your drug is not an endogenous substance, the differential equations for ADVAN2 with ALAG1 and D1 are shown below (using ADVAN6). Part 2) "I'm not very clear what's the meaning of D1 and KA when both are modeled." Based upon the ADVAN that you are using, NONMEM is putting the dose into the depot compartment as a constant rate infusion with a duration of D1 (hours, days, etc.). It starts the infusion into the depot compartment at time=ALAG1 (hours,days, etc.) after each dose. The dose is then transferred from the depot compartment to the central compartment using a first-order process (Ka 1/hr or 1/day, etc.) I hope this information helps, Luann Phillips --------------------------------------------- Example Code: $SUBROUTINES ADVAN6 TOL=5 $MODEL COMP=(DEPOT,DEFDOSE) COMP=(CENTRAL,DEFOBS) COMP=(PD1) etc. $PK KASC=THETA(4) VSC=THETA(5) CLSC=THETA(6) LGSC=THETA(8) MU_4=KASC MU_5=VSC MU_6=CLSC MU_8=THETA(11) SD=THETA(9) SIG=SD KA=EXP(MU_4+ETA(4)) V=EXP(MU_5+ETA(5)) CL=EXP(MU_6+ETA(6)) K=CL/V S2=V/1000; DOSE IN 1000 U, CONC in U, VOLUME IN mL ALAG1=LGSC*EXP(ETA(10)) D1=EXP(MU_8+ETA(8)) $DES DADT(1) = -KA*A(1) DADT(2) = KA*A(1) - K*A(2) DADT(3) = equations for PD cmt 1 etc. -------------------------------------------------- Xiao Hu wrote: > Dear NMusers, > > I'm using ADVAN2 to model the PK of a drug. To best fit the profile, the model includes ALAG1 and D1. For the next step, the ADVAN2 needs to be translated into differential equation to include a PD compartment. How should I write the differential equation for ALAG1 and D1? As you can see, there is Ka in the ADVAN2 model. I'm not very clear what's the meaning of D1 and KA when both are modeled. Any hint or previous link would be appreciated. Thanks in advance! > > $SUBROUTINES ADVAN2 > > $PK > > KASC=THETA(4) > VSC=THETA(5) > CLSC=THETA(6) > LGSC=THETA(8) > > MU_4=KASC > MU_5=VSC > MU_6=CLSC > MU_8=THETA(11) > > SD=THETA(9) > > SIG=SD > > KA=EXP(MU_4+ETA(4)) > V=EXP(MU_5+ETA(5)) > CL=EXP(MU_6+ETA(6)) > K=CL/V > S2=V/1000; DOSE IN 1000 U, CONC in U, VOLUME IN mL > ALAG1=LGSC*EXP(ETA(10)) > D1=EXP(MU_8+ETA(8)) > > Final parameter estimates: > > $THETA > 12 ;THETA5 > 8.89 ;THETA6 > 0.0015;THETA8 > > 0.263 ; THETA9 2.87; THETA11 > > Best regards, > Shelley > > ======================================== > Xiao Hu (Shelley), Ph.D. > Scientist, > Development Pharmacokinetics & Disposition > Biogen Idec, Inc. > 14 Cambridge Center > Cambridge, MA 02142