So, you want F1 to change while the infusion is on-going. In that case, I would use the same kind of MTIME-based code as you included in your original post.

From: "Bill Denney" <wden...@humanpredictions.com> To: "Sebastien Bihorel" <sebastien.biho...@cognigencorp.com> Cc: "NMUsers" <nmusers@globomaxnm.com> Sent: Tuesday, March 13, 2018 9:21:00 PM Subject: RE: [NMusers] Time-Varying Bioavailability on Zero-Order Infusion Hi Sebastien, Thanks for that suggestion! Unfortunately, that will only update when I have observation records, so it will change R1 in discrete steps at each observation (I could insert a lot of observations, but it still has the same limitation). I need it to continuously vary—this solution does that, but I’d like to learn a simpler way than what I suggested. Thanks, Bill From: Sebastien Bihorel < [ mailto:sebastien.biho...@cognigencorp.com | sebastien.biho...@cognigencorp.com ] > Sent: Tuesday, March 13, 2018 9:17 PM To: Bill Denney < [ mailto:wden...@humanpredictions.com | wden...@humanpredictions.com ] > Cc: NMUsers < [ mailto:nmusers@globomaxnm.com | nmusers@globomaxnm.com ] > Subject: Re: [NMusers] Time-Varying Bioavailability on Zero-Order Infusion Hi, I would suggest the following solution which should also work if you want to apply some covariate effect on bioavailability: * On the dataset side, set your RATE variable to -1 and store the actual infusion rates into another variable, eg IVRATE * On the model side: $PK ... ; assuming the IV infusion are made in compartment 1 F1 = <whatever time varying function> R1 = F1*IVRATE Voila, NONMEM should take care of the dosing in the background as usual. Sebastien From: "Bill Denney" < [ mailto:wden...@humanpredictions.com | wden...@humanpredictions.com ] > To: "NMUsers" < [ mailto:nmusers@globomaxnm.com | nmusers@globomaxnm.com ] > Sent: Tuesday, March 13, 2018 8:58:41 PM Subject: [NMusers] Time-Varying Bioavailability on Zero-Order Infusion Hi NONMEMers, Is there a good way to assign a time-varying bioavailabilty on a zero-order rate of infusion in NONMEM? The best I’ve been able to come up with is something like the below. It seems like something that should be easier than what I’m doing below (I adjusted it from the real example as I was typing it into the email—I could have introduced a bug in the process). And importantly, -9998 is well before any time in my database. (dosing into CMT=1 with an IV infusion) $MODEL COMP=(CENTRAL DEFDOSE DEFOBS) ; central COMP=(P1) ; peripheral 1 COMP=(P2) ; peripheral 2 $PK ; Normal stuff and ... ; Record the dosing time IF (NEWIND.LT.2) THEN TDOSE = -9999 DOSEEND = -9998 DOSE = -999 DOSERATE = 0 ENDIF IF ((EVID.EQ.1 .OR. EVID.EQ.4) .AND. RATE.GT.0) THEN TDOSE = TIME DOSEEND = TIME + AMT/RATE DOSERATE=RATE MTDIFF=1 ENDIF MTIME(1)=TDOSE MTIME(2)=DOSEEND F1 = 0 ; Bioavailability is zero so that the $DES block has full control over the rate. RATEADJTAU=THETA(10) RATEADJMAX=THETA(11) $DES ; Manually control the infusion RATEIN = 0 IF (MTIME(1).LE.T .AND. T.LE.MTIME(2)) THEN RATEADJCALC = RATEADJMAX * EXP(-(T – MTIME(1)) * RATEADJTAU) RATEIN = DOSERATE - RATEADJCALC ENDIF DADT(1) = RATEIN - K10*A(1) - K12*A(1) + K21*A(2) - K13*A(1) + K31*A(3) DADT(2) = K12*A(1) - K21*A(2) DADT(3) = K13*A(1) - K31*A(3) Thanks, Bill