-
Notifications
You must be signed in to change notification settings - Fork 5
/
Copy pathExecutable_run35b_ddm2.mod
207 lines (175 loc) · 5.23 KB
/
Executable_run35b_ddm2.mod
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
$PROBLEM GENTAMICIN model
;data from Nielsen2009, Thomson1988, Estonia_unpub
$INPUT ID GA GIRL TIME RATE EVID AMT WT CREAT DV PNA PMA TCREA OCC
;GA in weeks
;AMT in mg
;RATE in mg/h
;CREAT in umol/L
;PNA in days
;PMA in weeks
;WT in g
;TCREA = typical (for PMA) SCr: TCREA=PMA*(-2.8488)+166.48 [Cuzzolin 2006 and Rudd 1983]
;OCC=a dose with a subsequent level reported
$DATA simdataDDM.csv IGNORE=@
$SUBROUTINE ADVAN6 TOL=6
$MODEL
COMP=(CENTRAL)
COMP=(PERIPH1)
COMP=(PERIPH2)
COMP=(COVCMT1) ; PNA time-var. covariate compartment
COMP=(COVCMT2) ; CREATININE t-v. cov. compartment
$PK
; Three-comp model
IF(NEWIND.NE.2)OTIM1=0
IF(NEWIND.NE.2)OCOV1=0
IF(NEWIND.NE.2)OTIM2=0
IF(NEWIND.NE.2)OCOV2=0
;
STUDY=0
IF(ID.LT.2000) STUDY=1 ;Glasgow, Thomson1988
IF(ID.GE.2000.AND.ID.LT.3000) STUDY=2 ;Uppsala, Nielsen2009
IF(ID.GE.3000) STUDY=3 ;Estonia, unpublished
;
WTKG = WT/1000
;
T50 = THETA(7)
HILL = THETA(8)
MF = PMA**HILL/(PMA**HILL+T50**HILL)
;
CREAT2 = CREAT
IF(CREAT.LT.0) CREAT2 = TCREA ; when SCr is NA=-99, it is the typical SCr
;OF = (CREAT2/TCREA)**(THETA(9))
;
P50 = THETA(10)
;PNAF = PNA/(P50+PNA)
;
CRPWR = THETA(9)
;IOV code
BOVC = 0
IF(OCC.EQ.1) BOVC = ETA(7)
IF(OCC.EQ.2) BOVC = ETA(8)
IF(OCC.EQ.3) BOVC = ETA(9)
IF(OCC.EQ.4) BOVC = ETA(10)
IF(OCC.EQ.5) BOVC = ETA(11)
IF(OCC.EQ.6) BOVC = ETA(12)
IF(OCC.EQ.7) BOVC = ETA(13)
IF(OCC.EQ.8) BOVC = ETA(14)
IF(OCC.EQ.9) BOVC = ETA(15)
IF(OCC.EQ.10) BOVC = ETA(16)
IF(OCC.EQ.11) BOVC = ETA(17)
IF(OCC.EQ.12) BOVC = ETA(18)
IF(OCC.EQ.13) BOVC = ETA(19)
IF(OCC.EQ.14) BOVC = ETA(20)
IF(OCC.EQ.15) BOVC = ETA(21)
IF(OCC.EQ.16) BOVC = ETA(22)
IF(OCC.EQ.17) BOVC = ETA(23)
IF(OCC.EQ.18) BOVC = ETA(24)
IF(OCC.EQ.19) BOVC = ETA(25)
IF(OCC.EQ.20) BOVC = ETA(26)
IF(OCC.EQ.21) BOVC = ETA(27)
IF(OCC.EQ.22) BOVC = ETA(28)
;
TVCL = THETA(1)*MF*(WTKG/70)**(0.632) ; typical value of CL
TVV1 = THETA(2)*(WTKG/70) ; typical value of V1
TVQ = THETA(3)*(WTKG/70)**(0.75) ; ty. value of intercompartmental CL
TVV2 = THETA(4)*(WTKG/70) ; ty. value of V2
TVQ2 = THETA(5)*(WTKG/70)**(0.75) ; ty value of CL3
TVV3 = THETA(6)*(WTKG/70) ; ty value of V3
;
CL = TVCL*EXP(ETA(1)+BOVC) ; individual value of CL
V1 = TVV1*EXP(ETA(2))
Q = TVQ*EXP(ETA(3))
V2 = TVV2*EXP(ETA(4))
Q2 = TVQ2*EXP(ETA(5))
V3 = TVV3*EXP(ETA(6))
;
K = CL/V1
K12 = Q/V1
K21 = Q/V2
K13 = Q2/V1
K31 = Q2/V3
;
IF(EVID.EQ.1) TM=TIME
IF(EVID.EQ.1) TAD=0
IF(EVID.NE.1) TAD=TIME-TM
;
SL1 = 0
IF(TIME.GT.OTIM1) SL1 = (PNA-OCOV1)/(TIME-OTIM1)
A_0(4) = PNA
;
SL2 = 0
IF(TIME.GT.OTIM2) SL2 = (CREAT2-OCOV2)/(TIME-OTIM2)
A_0(5) = CREAT2
;
$DES
DADT(4)= SL1
TCOV1 = A(4)
DADT(5)= SL2
TCOV2 = A(5)
;PNAF = PNA/(P50+PNA)
PNAF = TCOV1/(P50+TCOV1)
;OF = (CREAT2/TCREA)**(THETA(9))
OF = (TCOV2/TCREA)**CRPWR
DADT(1) = A(3)*K31+A(2)*K21-A(1)*(K*PNAF*OF+K12+K13)
DADT(2) = A(1)*K12-A(2)*K21
DADT(3) = A(1)*K13-A(3)*K31
$ERROR
IPRED = A(1)/V1
Y = IPRED*(1+EPS(1)) + EPS(2)
OCOV1 = PNA
OTIM1 = TIME
OCOV2 = CREAT2
OTIM2 = TIME
$THETA (0,6.20684) ; 1. TVCL (lower bound,initial estimate)
$THETA (0,26.5004) ; 2. TVV1 (lower bound,initial estimate)
$THETA (0,2.15099) ; 3. TVQ
$THETA (0,21.151) ; 4. TVV2
$THETA (0,0.270697) ; 5. TVQ2
$THETA (0,147.893) ; 6. TVV3
$THETA 55.4 FIX ; 7. T50
$THETA 3.33 FIX ; 8. Hill
$THETA -0.129934 ; 9. power exponent on creatinine
$THETA (0,1.70302) ; 10. PNA50
$OMEGA BLOCK(2)
0.175278 ; variance for ETA(1), initial estimate
0.115896 0.112362 ; COvariance ETA(1)-ETA(2), var for ETA(2), initial estimate
$OMEGA 0 FIX
$OMEGA 0.131759
$OMEGA 0 FIX
$OMEGA 0.177214
$OMEGA BLOCK(1)
0.0140684 ; 7. IOV_CL
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME
$SIGMA 0.036033 ; variance PROP res error, initial estimate
$SIGMA 0.0164023
$ESTIMATION METHOD=1 INTER MAXEVAL=0 PRINT=1 ; calculation method
;$COVARIANCE ; standard error of estimate is calculated
$TABLE ID TIME IPRED DV CWRES
CL V1 Q V2 Q2 V3 ETA(1) ETA(2) ETA(3) ETA(4) ETA(5) ETA(6)
GA GIRL RATE EVID AMT WT CREAT PNA PMA TCREA OCC TAD STUDY
MF OF CREAT2 PNAF BOVC SL2 TCOV2 PNA SL1 TCOV1
TVCL TVV1 TVQ TVV2 TVQ2 TVV3 NOPRINT ONEHEADER FILE=sdtab35b_ddm2
;$TABLE ID WT GA PNA PMA CREAT TCREA NOPRINT NOAPPEND ONEHEADER FILE=cotab32
;$TABLE ID GIRL STUDY NOPRINT NOAPPEND ONEHEADER FILE=catab32
;$TABLE ID CL V ETA(1) ETA(2) NOPRINT NOAPPEND ONEHEADER FILE=patab27
;$SCAT DV VS PRED UNIT