stepwise zero order input
From: "Ralph Quadflieg" <quadflieg@uni-bonn.de>
Subject: stepwise zero order input
Date: Tue, 27 Oct 1998 14:45:00 +0100
Dear NONMEM user,
Here is the next problem with the stepwise zero order input:
; -------------2 COMP ADVAN 4 control-----------------------------------
$PROBLEM dissolution kinetics of 60mg diltiazem tablets uses PREDPP
$INPUT ID TIME DV AMT CMT PCMT EVID MDV RATE HGHT WGHT AGE Zeit FORM MALE
$DATA 605data IGNORE=#
$SUBROUTINES ADVAN4 TRANS1
$ABBREVIATED DERIV2=NOCOMMON
$PK
KA = THETA(10) * EXP(ETA(2))
V2 = THETA(11) * EXP(ETA(3))
CL23 = THETA(12) * WGHT * EXP(ETA(4))
V3 = THETA(13) * EXP(ETA(5))
CL20 = THETA(14) * WGHT * EXP(ETA(6))
F2 = THETA(15) * EXP(ETA(7))
; initializiation of concomittant time varying variables
Q1 = 0
Q2 = 0
Q3 = 0
Q4 = 0
Q5 = 0
Q6 = 0
Q7 = 0
Q8 = 0
Q9 = 0
; time varying variables
;1st day
IF (TIME.GT.0.AND.TIME.LE.30) Q1 = 1
IF (TIME.GT.30.AND.TIME.LE.60) Q2 = 1
IF (TIME.GT.60.AND.TIME.LE.120) Q3 = 1
IF (TIME.GT.120.AND.TIME.LE.180) Q4 = 1
IF (TIME.GT.180.AND.TIME.LE.240) Q5 = 1
IF (TIME.GT.240.AND.TIME.LE.300) Q6 = 1
IF (TIME.GT.300.AND.TIME.LE.360) Q7 = 1
IF (TIME.GT.360.AND.TIME.LE.390) Q1 = 1
IF (TIME.GT.390.AND.TIME.LE.420) Q2 = 1
IF (TIME.GT.420.AND.TIME.LE.480) Q3 = 1
IF (TIME.GT.480.AND.TIME.LE.540) Q4 = 1
IF (TIME.GT.540.AND.TIME.LE.600) Q5 = 1
IF (TIME.GT.600.AND.TIME.LE.660) Q6 = 1
IF (TIME.GT.660.AND.TIME.LE.720) Q7 = 1
IF (TIME.GT.720.AND.TIME.LE.750) Q1 = 1
IF (TIME.GT.750.AND.TIME.LE.780) Q2 = 1
IF (TIME.GT.780.AND.TIME.LE.840) Q3 = 1
IF (TIME.GT.840.AND.TIME.LE.900) Q4 = 1
IF (TIME.GT.900.AND.TIME.LE.960) Q5 = 1
IF (TIME.GT.960.AND.TIME.LE.1020) Q6 = 1
IF (TIME.GT.1020.AND.TIME.LE.1080) Q7 = 1
IF (TIME.GT.1080.AND.TIME.LE.1200) Q8 = 1
IF (TIME.GT.1200.AND.TIME.LE.1440) Q9 = 1
;2nd day
IF (TIME.GT.1440.AND.TIME.LE.1470) Q1 = 1
IF (TIME.GT.1470.AND.TIME.LE.1500) Q2 = 1
IF (TIME.GT.1500.AND.TIME.LE.1560) Q3 = 1
IF (TIME.GT.1560.AND.TIME.LE.1620) Q4 = 1
IF (TIME.GT.1620.AND.TIME.LE.1680) Q5 = 1
IF (TIME.GT.1680.AND.TIME.LE.1740) Q6 = 1
IF (TIME.GT.1740.AND.TIME.LE.1800) Q7 = 1
IF (TIME.GT.1800.AND.TIME.LE.1830) Q1 = 1
IF (TIME.GT.1830.AND.TIME.LE.1860) Q2 = 1
IF (TIME.GT.1860.AND.TIME.LE.1920) Q3 = 1
IF (TIME.GT.1920.AND.TIME.LE.1980) Q4 = 1
IF (TIME.GT.1980.AND.TIME.LE.2040) Q5 = 1
IF (TIME.GT.2040.AND.TIME.LE.2100) Q6 = 1
IF (TIME.GT.2100.AND.TIME.LE.2160) Q7 = 1
IF (TIME.GT.2160.AND.TIME.LE.2190) Q1 = 1
IF (TIME.GT.2190.AND.TIME.LE.2220) Q2 = 1
IF (TIME.GT.2220.AND.TIME.LE.2280) Q3 = 1
IF (TIME.GT.2280.AND.TIME.LE.2340) Q4 = 1
IF (TIME.GT.2340.AND.TIME.LE.2400) Q5 = 1
IF (TIME.GT.2400.AND.TIME.LE.2460) Q6 = 1
IF (TIME.GT.2460.AND.TIME.LE.2520) Q7 = 1
IF (TIME.GT.2520.AND.TIME.LE.2640) Q8 = 1
IF (TIME.GT.2640.AND.TIME.LE.2880) Q9 = 1
;3th day
IF (TIME.GT.2880.AND.TIME.LE.2910) Q1 = 1
IF (TIME.GT.2910.AND.TIME.LE.2940) Q2 = 1
IF (TIME.GT.2940.AND.TIME.LE.3000) Q3 = 1
IF (TIME.GT.3000.AND.TIME.LE.3060) Q4 = 1
IF (TIME.GT.3060.AND.TIME.LE.3120) Q5 = 1
IF (TIME.GT.3120.AND.TIME.LE.3180) Q6 = 1
IF (TIME.GT.3180.AND.TIME.LE.3240) Q7 = 1
IF (TIME.GT.3240.AND.TIME.LE.3270) Q1 = 1
IF (TIME.GT.3270.AND.TIME.LE.3300) Q2 = 1
IF (TIME.GT.3300.AND.TIME.LE.3360) Q3 = 1
IF (TIME.GT.3360.AND.TIME.LE.3420) Q4 = 1
IF (TIME.GT.3420.AND.TIME.LE.3480) Q5 = 1
IF (TIME.GT.3480.AND.TIME.LE.3540) Q6 = 1
IF (TIME.GT.3540.AND.TIME.LE.3600) Q7 = 1
IF (TIME.GT.3600.AND.TIME.LE.3630) Q1 = 1
IF (TIME.GT.3630.AND.TIME.LE.3660) Q2 = 1
IF (TIME.GT.3660.AND.TIME.LE.3720) Q3 = 1
IF (TIME.GT.3720.AND.TIME.LE.3780) Q4 = 1
IF (TIME.GT.3780.AND.TIME.LE.3840) Q5 = 1
IF (TIME.GT.3840.AND.TIME.LE.3900) Q6 = 1
IF (TIME.GT.3900.AND.TIME.LE.3960) Q7 = 1
IF (TIME.GT.3960.AND.TIME.LE.4080) Q8 = 1
IF (TIME.GT.4080.AND.TIME.LE.4320) Q9 = 1
;4th day
IF (TIME.GT.4320.AND.TIME.LE.4350) Q1 = 1
IF (TIME.GT.4350.AND.TIME.LE.4380) Q2 = 1
IF (TIME.GT.4380.AND.TIME.LE.4440) Q3 = 1
IF (TIME.GT.4440.AND.TIME.LE.4500) Q4 = 1
IF (TIME.GT.4500.AND.TIME.LE.4560) Q5 = 1
IF (TIME.GT.4560.AND.TIME.LE.4620) Q6 = 1
IF (TIME.GT.4620.AND.TIME.LE.4680) Q7 = 1
IF (TIME.GT.4680.AND.TIME.LE.4710) Q1 = 1
IF (TIME.GT.4710.AND.TIME.LE.4740) Q2 = 1
IF (TIME.GT.4740.AND.TIME.LE.4800) Q3 = 1
IF (TIME.GT.4800.AND.TIME.LE.4860) Q4 = 1
IF (TIME.GT.4860.AND.TIME.LE.4920) Q5 = 1
IF (TIME.GT.4920.AND.TIME.LE.4980) Q6 = 1
IF (TIME.GT.4980.AND.TIME.LE.5040) Q7 = 1
IF (TIME.GT.5040.AND.TIME.LE.5070) Q1 = 1
IF (TIME.GT.5070.AND.TIME.LE.5100) Q2 = 1
IF (TIME.GT.5100.AND.TIME.LE.5160) Q3 = 1
IF (TIME.GT.5160.AND.TIME.LE.5220) Q4 = 1
IF (TIME.GT.5220.AND.TIME.LE.5280) Q5 = 1
IF (TIME.GT.5280.AND.TIME.LE.5340) Q6 = 1
IF (TIME.GT.5340.AND.TIME.LE.5400) Q7 = 1
IF (TIME.GT.5400.AND.TIME.LE.5520) Q8 = 1
IF (TIME.GT.5520.AND.TIME.LE.5760) Q9 = 1
; rates with which drug is beeing dissoluted into gut compartment during time
; intervals
A1 = THETA(1) * EXP(ETA(1))
A2 = THETA(2) * EXP(ETA(1))
A3 = THETA(3) * EXP(ETA(1))
A4 = THETA(4) * EXP(ETA(1))
A5 = THETA(5) * EXP(ETA(1))
A6 = THETA(6) * EXP(ETA(1))
A7 = THETA(7) * EXP(ETA(1))
A8 = THETA(8) * EXP(ETA(1))
A9 = THETA(9) * EXP(ETA(1))
; fractional rates
FR1 = Q1 * A1
FR2 = Q2 * A2
FR3 = Q3 * A3
FR4 = Q4 * A4
FR5 = Q5 * A5
FR6 = Q6 * A6
FR7 = Q7 * A7
FR8 = Q8 * A8
FR9 = Q9 * A9
; rate
R1 = FR1+FR2+FR3+FR4+FR5+FR6+FR7+FR8+FR9
S2 = V2
K = CL20/V2
K23 = CL23/V2
K32 = CL23/V3
$ERROR
MEP = F
Y = MEP + (MEP*ERR(1))
$THETA NOABORT
(0, 2 , ) ; TV A1
(0, 3.2 , ) ; TV A2
(0, 60 , ) ; TV A3
(0, 6 , ) ; TV A4
(0, 12 , ) ; TV A5
(0, 10 , ) ; TV A6
(0, 0.3 , ) ; TV A7
(0, 0.3 , ) ; TV A8
(0, 0.1 , ) ; TV A9
( 0.0269 FIXED ) ; TVka
( 118 FIXED ) ; TVVc
( 0.0149 FIXED ) ; TVCL23/kg
( 281 FIXED ) ; TVV3
( 0.0142 FIXED ) ; TVCLe/kg
( 0.508 FIXED ) ; TVF2
$OMEGA
.25 ; Variance in r1
; .25 ; Variance in r2
; .25 ; Variance in r3
; .25 ; Variance in r4
; .25 ; Variance in r5
; .25 ; Variance in r6
; .25 ; Variance in r7
; .25 ; Variance in r8
( .320 ) ; Variance in ka
( .226 ) ; Variance in Vc
( .0611 ) ; Varianve in CL23
( .201 ) ; Variance in V3
( .0492 ) ; Variance in CLe
( .0405 ) ; Variance in F1
$SIGMA .25 ; Variance in individual ERROR
;$MSFI
$ESTIMATION PRINT=5 MAXEVALS=9999 NOABORT ;POSTHOC NOABORT
METHOD=CONDITIONAL
;$COVARIANCE
$TABLE ID R1 TIME DV PRED FILE = testtable
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