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