# [NMusers] Time-Varying Bioavailability on Zero-Order Infusion

From: Bill Denney <wdenney_at_humanpredictions.com>
Date: Tue, 13 Mar 2018 20:58:41 -0400

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 wit=
h 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 proce=
ss).
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 contro=
l
over the rate.

\$DES

; Manually control the infusion

RATEIN = 0

IF (MTIME(1).LE.T .AND. T.LE.MTIME(2)) THEN

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

Received on Tue Mar 13 2018 - 20:58:41 EDT

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