stepwise zero order process
From: Ralph Quadflieg <quadflieg@uni-bonn.de>
Subject: stepwise zero order process
Date: unknown (Between Sept 8, 1998 and Oct 7, 1998)
> Dear NONMEM users,
>
> First of all:
> Thank you Mrs.Boeckmann for your help, regarding the 4 compartment model.
> Now I have another problem:
>
> We try to model a stepwise zero order process into a dose compartment. I do
> know the total amount and the duration of the single steps.
> We wrote a PK block with a time varying value like this:
>
> $PK
> KA = 0.026 ; fixed disposition param.
> V2 = 118
> CL23 = 0.0149 * WGHT
> V3 = 281
> CL20 = 0.0142 * WGHT
>
> F1 = 0.508
>
> Q1 = 0
> Q2 = 0
> Q3 = 0
> Q4 = 0
> Q5 = 0
> Q6 = 0
> Q7 = 0
> Q8 = 0
> Q9 = 0
> Q10 = 0
> Q11 = 0
> Q12 = 0
> Q13 = 0
> Q14 = 0
> Q15 = 0
> Q16 = 0
> Q17 = 0
> Q18 = 0
> Q19 = 0
> Q20 = 0
> Q21 = 0
> Q22 = 0
> Q23 = 0
> Q24 = 0
> ; Q25 = 0
> ; Q26 = 0
>
> ; duration of single steps:
>
> IF (TIME.GT.0.AND.TIME.LE.2880) Q1 = 1
> IF (TIME.GT.2880.AND.TIME.LE.4320) Q2 = 1
> IF (TIME.GT.4320.AND.TIME.LE.4350) Q3 = 1
> IF (TIME.GT.4350.AND.TIME.LE.4380) Q4 = 1
> IF (TIME.GT.4380.AND.TIME.LE.4440) Q5 = 1
> IF (TIME.GT.4440.AND.TIME.LE.4500) Q6 = 1
> IF (TIME.GT.4500.AND.TIME.LE.4560) Q7 = 1
> IF (TIME.GT.4560.AND.TIME.LE.4620) Q8 = 1
> IF (TIME.GT.4620.AND.TIME.LE.4680) Q9 = 1
> IF (TIME.GT.4680.AND.TIME.LE.4710) Q10 = 1
> IF (TIME.GT.4710.AND.TIME.LE.4740) Q11 = 1
> IF (TIME.GT.4740.AND.TIME.LE.4800) Q12 = 1
> IF (TIME.GT.4800.AND.TIME.LE.4860) Q13 = 1
> IF (TIME.GT.4860.AND.TIME.LE.4920) Q14 = 1
> IF (TIME.GT.4920.AND.TIME.LE.4980) Q15 = 1
> IF (TIME.GT.4980.AND.TIME.LE.5040) Q16 = 1
> IF (TIME.GT.5040.AND.TIME.LE.5070) Q17 = 1
> IF (TIME.GT.5070.AND.TIME.LE.5100) Q18 = 1
> IF (TIME.GT.5100.AND.TIME.LE.5160) Q19 = 1
> IF (TIME.GT.5160.AND.TIME.LE.5220) Q20 = 1
> IF (TIME.GT.5220.AND.TIME.LE.5280) Q21 = 1
> IF (TIME.GT.5280.AND.TIME.LE.5400) Q22 = 1
> IF (TIME.GT.5400.AND.TIME.LE.5520) Q23 = 1
> IF (TIME.GT.5520.AND.TIME.LE.5760) Q24 = 1
>
> A1 = Q1*THETA(1) * EXP(ETA(1))
> A2 = Q2*THETA(2) * EXP(ETA(2))
> A3 = Q3*THETA(3) * EXP(ETA(3))
> A4 = Q4+THETA(4) * EXP(ETA(4))
> A5 = Q5*THETA(5) * EXP(ETA(5))
> A6 = Q6*THETA(6) * EXP(ETA(6))
> A7 = Q7*THETA(7) * EXP(ETA(7))
> A8 = Q8*THETA(8) * EXP(ETA(8))
> A9 = Q9*THETA(9) * EXP(ETA(9))
> A10 = Q10*THETA(10) * EXP(ETA(10))
> A11 = Q11*THETA(11) * EXP(ETA(11))
> A12 = Q12*THETA(12) * EXP(ETA(12))
> A13 = Q13*THETA(13) * EXP(ETA(13))
> A14 = Q14*THETA(14) * EXP(ETA(14))
> A15 = Q15*THETA(15) * EXP(ETA(15))
> A16 = Q16*THETA(16) * EXP(ETA(16))
> A17 = Q17*THETA(17) * EXP(ETA(17))
> A18 = Q18*THETA(18) * EXP(ETA(18))
> A19 = Q19*THETA(19) * EXP(ETA(19))
> A20 = Q20*THETA(20) * EXP(ETA(20))
> A21 = Q21*THETA(21) * EXP(ETA(21))
> A22 = Q21*THETA(22) * EXP(ETA(22))
> A23 = Q21*THETA(23) * EXP(ETA(23))
> A24 = Q21*THETA(24) * EXP(ETA(24))
> ; A25 = Q21*THETA(25) * EXP(ETA(25))
> ; A26 = Q21*THETA(26) * EXP(ETA(26))
>
> A= A1+A2+A3+A4+A5+A6+A7+A8+A9+A10+A11+A12+A13+A14
> B = A15+A16+A17+A18+A19+A20+A21+A22+A23+A24
>
> R1 = A + B ; rate parameter
> S2 = V2 ; ADVAN4 TRANS1
> K = CL20/V2
> K23 = CL23/V2
> K32 = CL23/V3
>
> in the data records the total AMT 720000 is in the first record (TIME = 0)
> and the RATE data item is -1 in this record.
>
> NOMEM does not fit single steps as I expected but something like a mean
> rate which leads to a constant steady state plasma level instead of fitting
> the whole plasma level time course.
>
> I thought that with my Qs only one THTEA is estimated during the time
> intervall, which seems not to be true.
>
> So how can a stepwise zero order process can be modeled with time varying
> concomittant variables ?
>
> Best regards and thank you in advance
>
> Ralph Quadflieg
> Dept.Pharm.Techn.Biopharm.
> University of Bonn
> An der Immenburg 4
> D-53121 Bonn
> Germany
> quadflieg@uni-bonn
> http://www.pharma.uni-bonn.de/pharmtech/
> Tel.: ++49 228 218997
> Fax.:++49 228 735268