Hello,
I think that the model that you refer to is called the KOKA absorption model
(Holford et al. J Pharmacokinet Biopharm. 1992; 20:421-42). You don't need
$DES, it can be easily coded using ADVAN4 (it will greatly reduce your run
time). I guess you know what fraction of the dose enters as a zero order
process and what remaining fraction enters as the first order process (I see
that you have KO in the code). The fraction that enters as the zero order
process is the THETA(2) in the code below. Moreover, you will need 2 dosing
records per dose that enters the system, see example dataset for 1 individual
below as well.
In my experience, the duration of the zero order input and its corresponding
fraction was unknown. You can even estimate these parameters. The only trick is
that if you estimate the fraction, please put THETA(2) inside a logit function
[you can find more details here: Samtani MN, Vermeulen A, Stuyckens, K.
Population pharmacokinetics of intramuscular paliperidone palmitate in patients
with schizophrenia. A novel once-monthly, long-acting formulation of an
atypical antipsychotic. Clin Pharmacokinet. 48: 585-600 (2009)]
Good luck,
Mahesh
_______________________________________________________________________________________________
$PK
CALLFL=-2
;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;; KA
TVKA=THETA(1)
KA =TVKA*EXP(ETA(1))
;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;; ALAG & DN
DUR = 2.99
D2 = DUR
ALAG1 = DUR
;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;; FN
TVF=THETA(2) ; replace THETA(2) with your known fraction.
F2 = TVF
F1 = 1-TVF
#ID TIME DV CMT AMT RATE
6001 0 0 1 10 0
6001 0 0 2 10 -2
6001 1 0.2 2 0 0
6001 6 1.9 2 0 0
6001 24 0.1 2 0 0
________________________________
From: owner-nmus...@globomaxnm.com on behalf of Liu Dongyang
Sent: Wed 4/6/2011 9:33 AM
To: nmusers
Subject: [NMusers] Two sequential absorption processes
Dear NonMEM users,
I want to code a two sequential absorption processes with 2 CMT: zero-order
absorption for the first 2.99 hours and then
first-order absorption for the rest time. My code is listed as below. My
question is when I change K0 (zero-order absorpption rate),
the predicted concentrations in the first 2.99 hours does not change. It seems
like AL is useless.
I am very appreciated if anyone can tell me the problem in my code or other
things. Thanks a lot!
$DES
IF (AMT.GT.0) THEN
TDOS=TIME ;dosing time
TL=TDOS+2.99 ;lag time=2.99 hour
ENDIF
AL=0
BL=0
K0=14100
IF (TIME .LE. TDOS) THEN ; for PD baseline
INPT=0
ELSE
IF (TIME .LE. TL .AND.TIME .GT. TDOS ) THEN
AL=1
ELSE
BL=1
ENDIF
ENDIF
INPT=AL*K0+BL*KA*A(1)
C2=A(2)/V1
C3=A(3)/V2
DADT(1) = -INPT
DADT(2) = INPT-CL*C2- CLD*(C2-C3)
DADT(3) = CLD*(C2-C3)
Best regards,
Liu, Dongyang, PhD, Postdoc Fellow
Department of Pharmaceutical sciences,
State University of New York at Buffalo.
Tel(o):01-716-645-4840,
Cell: 01-716-908-6644,
