PKSolver 2.

0 Non-Compartmental Analysis of Plasma Data after Intravenous Bolus Input

Time Unit h Method Linear Trapezoidal

Conc Unit μg/ml Analyst Irbah
Dose 100 Date 2018-5-9
Dose Unit μg Time 14:17:45

Time Conc ln(C) AUC AUMC R R_adj

0.5 6.243 1.83146084 3.38371768 0.780375 -0.9948014 0.98847767
1 5.345 1.67616154 6.28071768 2.897 -0.9963751 0.99185872
2 4.893 1.58780561 11.3997177 10.4625 -0.9967354 0.99255033
3 4.341 1.46810474 16.0167177 21.867 -0.9970075 0.99302792
8 3.2 1.16315081 34.8692177 118.4245 -0.9966263 0.9919167
12 2.803 1.03069027 46.8752177 236.8965 -0.9952968 0.98826963
24 1.566 0.4485246 73.0892177 664.2165 -0.9922304 0.97936158
36 1.025 0.02469261 88.6352177 1111.1205 -0.9848587 0.95491984
48 0.606 -0.5008753 98.4212177 1507.0485 -0.964114 0.85903145
60 0.317 -1.1488535 103.959218 1795.6965
72 0.252 -1.3783262 107.373218 2018.6805

5
Concentration (μg/ml)

0
0 10 20 30 40 50 60 70 80
Time (h)

10
Concentration (μg/ml)

1
Concentration (μg/m
1

0.1
0 10 20 30 40 50 60 70 80
Time (h)

10
Concentration (μg/ml)

0.1
0 10 20 30 40 50 60 70 80
Time (h)
venous Bolus Input

Parameter Unit Value

Lambda_z 1/h 0.042128189
t1/2 h 16.45328689
Tmax h 0.5
Cmax μg/ml 6.243
C0 μg/ml 7.29187072
Clast_obs/Cmax 0.040365209
AUC 0-t μg/ml*h 107.3732177
AUC 0-inf_obs μg/ml*h 113.3549607
AUC 0-t/0-inf_obs 0.947229985
AUMC 0-inf_obs μg/ml*h^2 2591.355081
MRT 0-inf_obs h 22.86053531
Vz_obs (μg)/(μg/ml) 20.94048223
Cl_obs (μg)/(μg/ml)/h 0.882184594
Vss_obs (μg)/(μg/ml) 20.16721206
PKSolver 2.0 Compartmental Analysis of Plasma Data after Intravenous Bolus Input

Time Unit h
Conc Unit μg/ml Analyst Irbah
Dose 100 Date 2018-5-9
Dose Unit μg Time 14:25:11

Time Conc ln(Conc) Conc_pre Residual Weight Parameter Unit

0.5 6.243 1.83146084 5.51304705 0.72995295 1 C0 μg/ml
1 5.345 1.67616154 5.35762503 -0.012625 1 k10 1/h
2 4.893 1.58780561 5.05980229 -0.1668023 1
3 4.341 1.46810474 4.77853509 -0.4375351 1 Parameter Unit
8 3.2 1.16315081 3.59005366 -0.3900537 1 t1/2 h
12 2.803 1.03069027 2.85591889 -0.0529189 1 V (μg)/(μg/ml)
24 1.566 0.4485246 1.43774099 0.12825901 1 CL (μg)/(μg/ml)/h
36 1.025 0.02469261 0.72379477 0.30120523 1 AUC 0-t μg/ml*h
48 0.606 -0.5008753 0.36437639 0.24162361 1 AUC 0-inf μg/ml*h
60 0.317 -1.1488535 0.18343619 0.13356381 1 AUMC μg/ml*h^2
72 0.252 -1.3783262 0.09234636 0.15965364 1 MRT h
Vss μg/(μg/ml)

Diagnostics Value
r obs-pre 0.989183978
SS 1.116078435
WSS 1.116078435
R^2 0.991574275
WR^2 0.991574275
SE 0.352148711
AIC 5.208032577
SC 6.003823122

10

Predicted
Observed

1
Concentration (μg/ml)

0.1
 1

Concentration (μg/m
0.1

0.01
0 10 20 30 40 50 60 70 80
Time (h)

Residual Plot
0.8

0.6

0.4
Residual (μg/ml)

0.2

0
0 10 20 30 40 50 60 70 80

-0.2

-0.4

-0.6
Time (h)
 Value Time Conc_Pre 7
5.672977785 0.5 5.51304705
0.057193377 1.22222222 5.28996244
6
1.94444444 5.07590492
Value 2.66666667 4.87050921
12.11936104 3.38888889 4.6734248 5
17.62742669 4.11111111 4.48431538

Concentration (μg/ml)
1.008172054 4.83333333 4.30285824
4
97.57478487 5.55555556 4.12874374
99.18941874 6.27777778 3.96167475
1734.281565 7 3.80136619 3
17.48454207 7.72222222 3.64754449
17.62742669 8.44444444 3.49994716
9.16666667 3.35832233 2
9.88888889 3.22242833
10.6111111 3.09203326 1
11.3333333 2.96691461
12.0555556 2.84685886
12.7777778 2.73166115 0
13.5 2.6211249 0 10 20 30 40 50 60
14.2222222 2.51506148 Time (h)
14.9444444 2.41328991
15.6666667 2.3156365
16.3888889 2.22193462
17.1111111 2.13202438
17.8333333 2.04575234
18.5555556 1.96297128
19.2777778 1.88353995
20 1.80732279
20.7222222 1.73418975
21.4444444 1.66401603
22.1666667 1.59668187
22.8888889 1.53207239
23.6111111 1.47007731
24.3333333 1.41059086
25.0555556 1.35351151
25.7777778 1.29874188
26.5 1.24618849
27.2222222 1.19576166
27.9444444 1.14737535
28.6666667 1.10094698
29.3888889 1.05639733
30.1111111 1.01365037
30.8333333 0.97263316
31.5555556 0.93327571
32.2777778 0.89551085
 33 0.85927414
33.7222222 0.82450375
34.4444444 0.79114033
35.1666667 0.75912695
35.8888889 0.728409
36.6111111 0.69893404
37.3333333 0.67065178
38.0555556 0.64351396
38.7777778 0.61747427
39.5 0.59248826
40.2222222 0.56851332
40.9444444 0.54550851
41.6666667 0.52343459
42.3888889 0.50225389
43.1111111 0.48193027
43.8333333 0.46242903
44.5555556 0.44371691
45.2777778 0.42576197
46 0.40853358
46.7222222 0.39200233
47.4444444 0.37614002
48.1666667 0.36091957
48.8888889 0.34631501
49.6111111 0.33230143
50.3333333 0.3188549
51.0555556 0.30595249
51.7777778 0.29357217
52.5 0.28169281
53.2222222 0.27029416
53.9444444 0.25935675
54.6666667 0.24886192
55.3888889 0.23879176
56.1111111 0.22912908
56.8333333 0.21985741
57.5555556 0.21096091
58.2777778 0.20242441
59 0.19423334
59.7222222 0.18637372
60.4444444 0.17883213
61.1666667 0.17159572
61.8888889 0.16465212
62.6111111 0.1579895
63.3333333 0.15159648
64.0555556 0.14546215
64.7777778 0.13957605
65.5 0.13392812
66.2222222 0.12850874
66.9444444 0.12330866
67.6666667 0.11831899
68.3888889 0.11353123
69.1111111 0.10893721
69.8333333 0.10452908
70.5555556 0.10029933
71.2777778 0.09624073
72 0.09234636
 Predicted
Observed

40 50 60 70 80
Time (h)
PKSolver 2.0 Compartmental Analysis of Plasma Data after Intravenous Bolus Input

Time Unit h
Conc Unit μg/ml Analyst Irbah
Dose 100 Date 2018-5-9
Dose Unit μg Time 14:26:32

Time Conc ln(Conc) Conc_pre Residual Weight Parameter Unit

0.5 6.243 1.83146084 6.14894708 0.09405292 1 A μg/ml
1 5.345 1.67616154 5.54587591 -0.2008759 1 Alpha 1/h
2 4.893 1.58780561 4.77022793 0.12277207 1 B μg/ml
3 4.341 1.46810474 4.31214995 0.02885005 1 Beta 1/h
8 3.2 1.16315081 3.27799276 -0.0779928 1
12 2.803 1.03069027 2.75284268 0.05015732 1 Parameter Unit
24 1.566 0.4485246 1.63867082 -0.0726708 1 k10 1/h
36 1.025 0.02469261 0.97555006 0.04944994 1 k12 1/h
48 0.606 -0.5008753 0.58077432 0.02522568 1 k21 1/h
60 0.317 -1.1488535 0.34575244 -0.0287524 1 t1/2Alpha h
72 0.252 -1.3783262 0.20583684 0.04616316 1 t1/2Beta h
C0 μg/ml
V (μg)/(μg/ml)
7 CL (μg)/(μg/ml)/h
V2 (μg)/(μg/ml)
Predicted CL2 (μg)/(μg/ml)/h
6
Observed AUC 0-t μg/ml*h
AUC 0-inf μg/ml*h
5
AUMC μg/ml*h^2
Concentration (μg/ml)

MRT h
4 Vss μg/(μg/ml)

3 Diagnostics Value
r obs-pre 0.99910604
2 SS 0.0850214368
WSS 0.0850214368
R^2 0.999358139
1
WR^2 0.999358139
SE 0.1102085275
0 AIC -19.113370426
0 10 20 30 40 50 60 70 80 SC -17.52178933
Time (h)

10

Predicted
Observed
Concentration (μg/ml)

1
Concentration (μg/m
1

0.1
0 10 20 30 40 50 60 70 80
Time (h)

Residual Plot
0.15

0.1

0.05
Residual (μg/ml)

0
0 10 20 30 40 50 60 70 80
-0.05

-0.1

-0.15

-0.2

-0.25
Time (h)
 Value Time Conc_Pre
2.359919721 0.5 6.14894708
0.747181035 1.22222222 5.33252705
4.623554869 1.94444444 4.8028666
0.043219935 2.66666667 4.44202737
3.38888889 4.18120487
Value 4.11111111 3.98023941
0.063407854 4.83333333 3.81567171
0.217701066 5.55555556 3.67377966
0.50929205 6.27777778 3.54651897
0.927683049 7 3.42915675
16.03767284 7.72222222 3.3188918
6.983474589 8.44444444 3.21405035
14.31951942 9.16666667 3.11361714
0.907969995 9.88888889 3.016962
6.12099609 10.6111111 2.92368041
3.117374646 11.3333333 2.8335006
105.3732541 12.0555556 2.74622921
110.135798 12.7777778 2.66171974
2479.412865 13.5 2.579854
22.51232487 14.2222222 2.50053132
20.44051551 14.9444444 2.42366223
15.6666667 2.34916472
16.3888889 2.27696207
17.1111111 2.2069815
17.8333333 2.13915342
18.5555556 2.07341092
19.2777778 2.00968945
20 1.94792665
20.7222222 1.88806217
21.4444444 1.83003758
22.1666667 1.7737963
22.8888889 1.71928347
23.6111111 1.66644598
24.3333333 1.61523231
25.0555556 1.56559256
25.7777778 1.51747836
26.5 1.47084282
27.2222222 1.4256405
27.9444444 1.38182734
28.6666667 1.33936067
29.3888889 1.29819909
30.1111111 1.2583025
30.8333333 1.21963202
31.5555556 1.18214998
32.2777778 1.14581984
 33 1.11060621
33.7222222 1.07647477
34.4444444 1.04339227
35.1666667 1.01132647
35.8888889 0.98024613
36.6111111 0.95012095
37.3333333 0.92092159
38.0555556 0.89261959
38.7777778 0.86518737
39.5 0.83859821
40.2222222 0.81282619
40.9444444 0.78784621
41.6666667 0.76363392
42.3888889 0.74016572
43.1111111 0.71741876
43.8333333 0.69537086
44.5555556 0.67400054
45.2777778 0.65328698
46 0.63321
46.7222222 0.61375003
47.4444444 0.5948881
48.1666667 0.57660585
48.8888889 0.55888545
49.6111111 0.54170964
50.3333333 0.52506168
51.0555556 0.50892535
51.7777778 0.49328492
52.5 0.47812516
53.2222222 0.4634313
53.9444444 0.44918901
54.6666667 0.43538441
55.3888889 0.42200407
56.1111111 0.40903493
56.8333333 0.39646436
57.5555556 0.38428012
58.2777778 0.37247032
59 0.36102347
59.7222222 0.3499284
60.4444444 0.33917431
61.1666667 0.32875072
61.8888889 0.31864747
62.6111111 0.30885471
63.3333333 0.29936291
64.0555556 0.29016281
64.7777778 0.28124545
65.5 0.27260214
66.2222222 0.26422447
66.9444444 0.25610425
67.6666667 0.24823359
68.3888889 0.24060481
69.1111111 0.23321048
69.8333333 0.2260434
70.5555556 0.21909657
71.2777778 0.21236324
72 0.20583684
0.5 6.243
1 5.345
2 4.893
3 4.341
8 3.2
12 2.803
24 1.566
36 1.025
48 0.606
60 0.317
72 0.252
PKSolver 2.0 Non-Compartmental Analysis of Plasma Data after Intravenous Bolus Input

Time Unit h Method Linear Trapezoidal

Conc Unit mg/ml Analyst Penori
Dose 5 Date 2018-5-9
Dose Unit mg Time 14:43:44

Time Conc ln(C) AUC AUMC R R_adj

15 138.59 4.93151993 2538.58111 15591.375 -0.9344495 0.83092779
30 96.09 4.56528525 4298.68111 52803 -0.9906645 0.97212416
45 86.204 4.45671658 5665.88611 103517.1 -0.9873632 0.94977199
60 75.909 4.32953525 6881.73361 166770
90 65.886 4.18792598 9008.65861 324034.2

160

140

120
Concentration (mg/ml)

100

80

60

40

20

0
10 20 30 40 50 60 70 80 90 100
Time (h)

1000

100
Concentration (mg/ml)

10

1
10 20 30 40 50 60 70 80 90 100
Time (h)
 10

Co
1
10 20 30 40 50 60 70 80 90 100
Time (h)

1000

100
Concentration (mg/ml)

10

1
10 20 30 40 50 60 70 80 90 100
Time (h)
venous Bolus Input

Parameter Unit Value

Lambda_z 1/h 0.006297671
t1/2 h 110.0640443
Tmax h 15
Cmax mg/ml 138.59
C0 mg/ml 199.8874815
Clast_obs/Cmax 0.475402266
AUC 0-t mg/ml*h 9008.658611
AUC 0-inf_obs mg/ml*h 19470.62084
AUC 0-t/0-inf_obs 0.462679577
AUMC 0-inf_obs mg/ml*h^2 2926853.76
MRT 0-inf_obs h 150.3215426
Vz_obs (mg)/(mg/ml) 0.040776525
Cl_obs (mg)/(mg/ml)/h 0.000256797
Vss_obs (mg)/(mg/ml) 0.038602144
PKSolver 2.0 Compartmental Analysis of Plasma Data after Intravenous Bolus Input

Time Unit h
Conc Unit mg/ml Analyst Penori
Dose 5 Date 2018-5-9
Dose Unit mg Time 14:44:22

Time Conc ln(Conc) Conc_pre Residual Weight Parameter Unit

0.5 6.243 1.83146084 5.51304705 0.72995295 1 C0 mg/ml
1 5.345 1.67616154 5.35762503 -0.012625 1 k10 1/h
2 4.893 1.58780561 5.05980229 -0.1668023 1
3 4.341 1.46810474 4.77853509 -0.4375351 1 Parameter Unit
8 3.2 1.16315081 3.59005366 -0.3900537 1 t1/2 h
12 2.803 1.03069027 2.85591889 -0.0529189 1 V (mg)/(mg/ml)
24 1.566 0.4485246 1.43774099 0.12825901 1 CL (mg)/(mg/ml)/h
36 1.025 0.02469261 0.72379477 0.30120523 1 AUC 0-t mg/ml*h
48 0.606 -0.5008753 0.36437639 0.24162361 1 AUC 0-inf mg/ml*h
60 0.317 -1.1488535 0.18343619 0.13356381 1 AUMC mg/ml*h^2
72 0.252 -1.3783262 0.09234636 0.15965364 1 MRT h
Vss mg/(mg/ml)

Diagnostics Value
7 r obs-pre 0.9891839777
SS 1.1160784345
Predicted WSS 1.1160784345
6
Observed R^2 0.9915742753
WR^2 0.9915742753
5
SE 0.3521487114
Concentration (mg/ml)

AIC 5.2080325767
4 SC 6.0038231223

0
0 10 20 30 40 50 60 70 80
Time (h)

10

Predicted
Observed

1
Concentration (mg/ml)

0.1
 1

Concentration (mg/
0.1

0.01
0 10 20 30 40 50 60 70 80
Time (h)

Residual Plot
0.8

0.6

0.4
Residual (mg/ml)

0.2

0
0 10 20 30 40 50 60 70 80

-0.2

-0.4

-0.6
Time (h)
 Value Time Conc_Pre
5.672977785 0.5 5.51304705
0.057193377 1.22222222 5.28996244
1.94444444 5.07590492
Value 2.66666667 4.87050921
12.11936104 3.38888889 4.6734248
0.881371334 4.11111111 4.48431538
0.050408603 4.83333333 4.30285824
97.57478487 5.55555556 4.12874374
99.18941874 6.27777778 3.96167475
1734.281565 7 3.80136619
17.48454207 7.72222222 3.64754449
0.881371334 8.44444444 3.49994716
9.16666667 3.35832233
9.88888889 3.22242833
10.6111111 3.09203326
11.3333333 2.96691461
12.0555556 2.84685886
12.7777778 2.73166115
13.5 2.6211249
14.2222222 2.51506148
14.9444444 2.41328991
15.6666667 2.3156365
16.3888889 2.22193462
17.1111111 2.13202438
17.8333333 2.04575234
18.5555556 1.96297128
19.2777778 1.88353995
20 1.80732279
20.7222222 1.73418975
21.4444444 1.66401603
22.1666667 1.59668187
22.8888889 1.53207239
23.6111111 1.47007731
24.3333333 1.41059086
25.0555556 1.35351151
25.7777778 1.29874188
26.5 1.24618849
27.2222222 1.19576166
27.9444444 1.14737535
28.6666667 1.10094698
29.3888889 1.05639733
30.1111111 1.01365037
30.8333333 0.97263316
31.5555556 0.93327571
32.2777778 0.89551085
 33 0.85927414
33.7222222 0.82450375
34.4444444 0.79114033
35.1666667 0.75912695
35.8888889 0.728409
36.6111111 0.69893404
37.3333333 0.67065178
38.0555556 0.64351396
38.7777778 0.61747427
39.5 0.59248826
40.2222222 0.56851332
40.9444444 0.54550851
41.6666667 0.52343459
42.3888889 0.50225389
43.1111111 0.48193027
43.8333333 0.46242903
44.5555556 0.44371691
45.2777778 0.42576197
46 0.40853358
46.7222222 0.39200233
47.4444444 0.37614002
48.1666667 0.36091957
48.8888889 0.34631501
49.6111111 0.33230143
50.3333333 0.3188549
51.0555556 0.30595249
51.7777778 0.29357217
52.5 0.28169281
53.2222222 0.27029416
53.9444444 0.25935675
54.6666667 0.24886192
55.3888889 0.23879176
56.1111111 0.22912908
56.8333333 0.21985741
57.5555556 0.21096091
58.2777778 0.20242441
59 0.19423334
59.7222222 0.18637372
60.4444444 0.17883213
61.1666667 0.17159572
61.8888889 0.16465212
62.6111111 0.1579895
63.3333333 0.15159648
64.0555556 0.14546215
64.7777778 0.13957605
65.5 0.13392812
66.2222222 0.12850874
66.9444444 0.12330866
67.6666667 0.11831899
68.3888889 0.11353123
69.1111111 0.10893721
69.8333333 0.10452908
70.5555556 0.10029933
71.2777778 0.09624073
72 0.09234636
PKSolver 2.0 Compartmental Analysis of Plasma Data after Intravenous Bolus Input

Time Unit h
Conc Unit mg/ml Analyst Penori
Dose 5 Date 2018-5-9
Dose Unit mg Time 14:45:29

Time Conc ln(Conc) Conc_pre Residual Weight Parameter Unit

0.5 6.243 1.83146084 6.14894708 0.09405292 1 A mg/ml
1 5.345 1.67616154 5.54587591 -0.2008759 1 Alpha 1/h
2 4.893 1.58780561 4.77022793 0.12277207 1 B mg/ml
3 4.341 1.46810474 4.31214995 0.02885005 1 Beta 1/h
8 3.2 1.16315081 3.27799276 -0.0779928 1
12 2.803 1.03069027 2.75284268 0.05015732 1 Parameter Unit
24 1.566 0.4485246 1.63867082 -0.0726708 1 k10 1/h
36 1.025 0.02469261 0.97555006 0.04944994 1 k12 1/h
48 0.606 -0.5008753 0.58077432 0.02522568 1 k21 1/h
60 0.317 -1.1488535 0.34575244 -0.0287524 1 t1/2Alpha h
72 0.252 -1.3783262 0.20583684 0.04616316 1 t1/2Beta h
C0 mg/ml
V (mg)/(mg/ml)
CL (mg)/(mg/ml)/h
7
V2 (mg)/(mg/ml)
Predicted CL2 (mg)/(mg/ml)/h
6 AUC 0-t mg/ml*h
Observed
AUC 0-inf mg/ml*h
5 AUMC mg/ml*h^2
Concentration (mg/ml)

MRT h
Vss mg/(mg/ml)
4

Diagnostics Value
3 r obs-pre 0.99910604
SS 0.0850214368
2 WSS 0.0850214368
R^2 0.999358139
WR^2 0.999358139
1 SE 0.1102085275
AIC -19.113370426
0 SC -17.521789335
0 10 20 30 40 50 60 70 80
Time (h)

10

Predicted
Observed
Concentration (mg/ml)

1
Concentration (mg/
1

0.1
0 10 20 30 40 50 60 70 80
Time (h)

Residual Plot
0.15

0.1

0.05
Residual (mg/ml)

0
0 10 20 30 40 50 60 70 80
-0.05

-0.1

-0.15

-0.2

-0.25
Time (h)
 Value Time Conc_Pre
2.359919721 0.5 6.14894708
0.747181035 1.22222222 5.33252705
4.623554869 1.94444444 4.8028666
0.043219935 2.66666667 4.44202737
3.38888889 4.18120487
Value 4.11111111 3.98023941
0.063407854 4.83333333 3.81567171
0.217701066 5.55555556 3.67377966
0.50929205 6.27777778 3.54651897
0.927683049 7 3.42915675
16.03767284 7.72222222 3.3188918
6.983474589 8.44444444 3.21405035
0.715975971 9.16666667 3.11361714
0.0453985 9.88888889 3.016962
0.306049805 10.6111111 2.92368041
0.155868732 11.3333333 2.8335006
105.3732541 12.0555556 2.74622921
110.135798 12.7777778 2.66171974
2479.412865 13.5 2.579854
22.51232487 14.2222222 2.50053132
1.022025776 14.9444444 2.42366223
15.6666667 2.34916472
16.3888889 2.27696207
17.1111111 2.2069815
17.8333333 2.13915342
18.5555556 2.07341092
19.2777778 2.00968945
20 1.94792665
20.7222222 1.88806217
21.4444444 1.83003758
22.1666667 1.7737963
22.8888889 1.71928347
23.6111111 1.66644598
24.3333333 1.61523231
25.0555556 1.56559256
25.7777778 1.51747836
26.5 1.47084282
27.2222222 1.4256405
27.9444444 1.38182734
28.6666667 1.33936067
29.3888889 1.29819909
30.1111111 1.2583025
30.8333333 1.21963202
31.5555556 1.18214998
32.2777778 1.14581984
 33 1.11060621
33.7222222 1.07647477
34.4444444 1.04339227
35.1666667 1.01132647
35.8888889 0.98024613
36.6111111 0.95012095
37.3333333 0.92092159
38.0555556 0.89261959
38.7777778 0.86518737
39.5 0.83859821
40.2222222 0.81282619
40.9444444 0.78784621
41.6666667 0.76363392
42.3888889 0.74016572
43.1111111 0.71741876
43.8333333 0.69537086
44.5555556 0.67400054
45.2777778 0.65328698
46 0.63321
46.7222222 0.61375003
47.4444444 0.5948881
48.1666667 0.57660585
48.8888889 0.55888545
49.6111111 0.54170964
50.3333333 0.52506168
51.0555556 0.50892535
51.7777778 0.49328492
52.5 0.47812516
53.2222222 0.4634313
53.9444444 0.44918901
54.6666667 0.43538441
55.3888889 0.42200407
56.1111111 0.40903493
56.8333333 0.39646436
57.5555556 0.38428012
58.2777778 0.37247032
59 0.36102347
59.7222222 0.3499284
60.4444444 0.33917431
61.1666667 0.32875072
61.8888889 0.31864747
62.6111111 0.30885471
63.3333333 0.29936291
64.0555556 0.29016281
64.7777778 0.28124545
65.5 0.27260214
66.2222222 0.26422447
66.9444444 0.25610425
67.6666667 0.24823359
68.3888889 0.24060481
69.1111111 0.23321048
69.8333333 0.2260434
70.5555556 0.21909657
71.2777778 0.21236324
72 0.20583684
15 138.59
30 96.09
45 86.204
60 75.909
90 65.886
PKSolver 2.0 Non-Compartmental Analysis of Plasma Data after Extravascular Input

Time Unit h Method Linear Trapezoidal

Conc Unit mg/ml Analyst Penori
Dose 100 Date 2018-5-9
Dose Unit mg Time 14:48:06

Time Conc ln(C) AUC AUMC R R_adj

0.5 2.75 1.01160091 0.6875 0.34375
1 6.24 1.83098018 2.935 2.2475
1.5 8.5 2.14006616 6.62 6.995
2 9.81 2.28340227 11.1975 15.0875 -0.9997928 0.99944753
3 7.43 2.00552586 19.8175 36.0425 -0.9997197 0.99915922
4 5.6 1.7227666 26.3325 58.3875 -0.9996426 0.99857047
6 3.19 1.16002092 35.1225 99.9275
8 1.91 0.64710324 40.2225 134.3475

12

10

8
Concentration (mg/ml)

0
0 1 2 3 4 5 6 7 8 9
Time (h)

10
Concentration (mg/ml)

1
Concentrati

1
0 1 2 3 4 5 6 7 8 9
Time (h)

10
Concentration (mg/ml)

1
0 1 2 3 4 5 6 7 8 9
Time (h)
avascular Input

Parameter Unit Value

Lambda_z 1/h 0.273929609
t1/2 h 2.530384292
Tmax h 2
Cmax mg/ml 9.81
Tlag h 0
Clast_obs/Cmax 0.194699286
AUC 0-t mg/ml*h 40.2225
AUC 0-inf_obs mg/ml*h 47.19509418
AUC 0-t/0-inf_obs 0.852260191
AUMC 0-inf_obs mg/ml*h^2 215.5822166
MRT 0-inf_obs h 4.567894615
Vz/F_obs (mg)/(mg/ml) 7.735068512
Cl/F_obs (mg)/(mg/ml)/h 2.118864296
PKSolver 2.0 Compartmental Analysis of Plasma Data after Extravascular Input

Time Unit h
Conc Unit mg/ml Analyst Penori
Dose 100 Date 2018-5-9
Dose Unit mg Time 14:50:16

Time Conc ln(Conc) Conc_pre Residual Weight Parameter Unit

0.5 2.75 1.01160091 4.33459292 -1.5845929 1 A mg/ml
1 6.24 1.83098018 6.78255516 -0.5425552 1 ka 1/h
1.5 8.5 2.14006616 7.95992928 0.54007072 1 k10 1/h
2 9.81 2.28340227 8.30390087 1.50609913 1
3 7.43 2.00552586 7.6255402 -0.1955402 1 Parameter Unit
4 5.6 1.7227666 6.22507967 -0.6250797 1 t1/2ka h
6 3.19 1.16002092 3.5012436 -0.3112436 1 t1/2k10 h
8 1.91 0.64710324 1.75105766 0.15894234 1 V/F (mg)/(mg/ml)
CL/F (mg)/(mg/ml)/h
Tmax h
Cmax mg/ml
AUC 0-t mg/ml*h
12 AUC 0-inf mg/ml*h
AUMC mg/ml*h^2
Predicted
MRT h
10
Observed
Diagnostics Value
Concentration (mg/ml)

8 r obs-pre 0.9572490267
SS 5.9164076059
WSS 5.9164076059
6
R^2 0.9812401047
WR^2 0.9812401047
4 SE 1.087787443
AIC 20.2218355311
SC 20.4601601561
2

0
0 1 2 3 4 5 6 7 8 9
Time (h)

10

Predicted
Observed
Concentration (mg/ml)

1
Concentrati

1
0 1 2 3 4 5 6 7 8 9
Time (h)

Residual Plot
2

1.5

1
Residual (mg/ml)

0.5

0
0 1 2 3 4 5 6 7 8 9
-0.5

-1

-1.5

-2
Time (h)
 Value Time Conc_Pre
340.2603612 0 0
0.507191142 0.08080808 0.8605966
0.474625358 0.16161616 1.65425256
0.24242424 2.38487444
Value 0.32323232 3.05616608
1.366638973 0.4040404 3.67163846
1.460409075 0.48484848 4.23461912
4.577188225 0.56565657 4.74826109
2.172449601 0.64646465 5.21555148
2.037788055 0.72727273 5.6393196
8.305346096 0.80808081 6.0222447
41.54568661 0.88888889 6.36686342
46.0309873 0.96969697 6.67557678
187.740521 1.05050505 6.95065693
4.078568199 1.13131313 7.19425353
1.21212121 7.40839986
1.29292929 7.5950186
1.37373737 7.75592738
1.45454545 7.89284406
1.53535354 8.0073917
1.61616162 8.10110338
1.6969697 8.17542671
1.77777778 8.23172821
1.85858586 8.27129738
1.93939394 8.29535066
2.02020202 8.30503515
2.1010101 8.30143216
2.18181818 8.28556063
2.26262626 8.25838028
2.34343434 8.22079474
2.42424242 8.17365444
2.50505051 8.11775938
2.58585859 8.05386177
2.66666667 7.98266853
2.74747475 7.9048437
2.82828283 7.82101067
2.90909091 7.73175439
2.98989899 7.63762337
3.07070707 7.53913164
3.15151515 7.43676064
3.23232323 7.33096092
3.31313131 7.22215388
3.39393939 7.11073328
3.47474747 6.99706683
3.55555556 6.88149759
3.63636364 6.76434529
3.71717172 6.64590771
3.7979798 6.52646183
3.87878788 6.40626504
3.95959596 6.28555623
4.04040404 6.16455685
4.12121212 6.04347187
4.2020202 5.9224908
4.28282828 5.80178851
4.36363636 5.68152611
4.44444444 5.56185177
4.52525253 5.44290145
4.60606061 5.32479968
4.68686869 5.20766017
4.76767677 5.09158654
4.84848485 4.97667286
4.92929293 4.8630043
5.01010101 4.75065764
5.09090909 4.63970181
5.17171717 4.53019838
5.25252525 4.42220203
5.33333333 4.31576099
5.41414141 4.21091747
5.49494949 4.10770803
5.57575758 4.00616399
5.65656566 3.90631175
5.73737374 3.80817315
5.81818182 3.71176577
5.8989899 3.61710324
5.97979798 3.52419551
6.06060606 3.43304911
6.14141414 3.34366742
6.22222222 3.2560509
6.3030303 3.1701973
6.38383838 3.08610189
6.46464646 3.00375762
6.54545455 2.92315535
6.62626263 2.84428401
6.70707071 2.76713074
6.78787879 2.69168108
6.86868687 2.6179191
6.94949495 2.54582752
7.03030303 2.47538786
7.11111111 2.40658057
7.19191919 2.33938511
7.27272727 2.27378006
7.35353535 2.20974325
7.43434343 2.14725182
7.51515152 2.08628233
7.5959596 2.02681082
7.67676768 1.96881289
7.75757576 1.91226379
7.83838384 1.85713845
7.91919192 1.80341157
8 1.75105766
PKSolver 2.0 Non-Compartmental Analysis of Plasma Data after Intravenous Bolus Input

Time Unit h Method Linear Trapezoidal

Conc Unit mg/ml Analyst Penori
Dose 200 Date 2018-5-9
Dose Unit mg Time 14:53:57

Time Conc ln(C) AUC AUMC R R_adj

0.5 5.31 1.66959184 2.85326299 0.66375 -0.9999942 0.99998644
1 4.62 1.53039471 5.33576299 2.4825 -0.9999929 0.99998301
1.5 4.02 1.3912819 7.49576299 5.145 -0.9999911 0.9999777
2 3.5 1.25276297 9.37576299 8.4025 -0.9999882 0.99996845
3 2.65 0.97455964 12.450763 15.8775 -0.9999818 0.99994539
4 2.01 0.69813472 14.780763 23.8725 -0.9999728 0.9998913
6 1.16 0.14842001 17.950763 38.8725
8 0.66 -0.4155154 19.770763 51.1125

4
Concentration (mg/ml)

0
0 1 2 3 4 5 6 7 8 9
Time (h)

10
Concentration (mg/ml)

0.1
 1

Concentrati

0.1
0 1 2 3 4 5 6 7 8 9
Time (h)

10
Concentration (mg/ml)

0.1
0 1 2 3 4 5 6 7 8 9
Time (h)
venous Bolus Input

Parameter Unit Value

Lambda_z 1/h 0.277521768
t1/2 h 2.497631751
Tmax h 0.5
Cmax mg/ml 5.31
C0 mg/ml 6.103051948
Clast_obs/Cmax 0.124293785
AUC 0-t mg/ml*h 19.77076299
AUC 0-inf_obs mg/ml*h 22.14895481
AUC 0-t/0-inf_obs 0.892627357
AUMC 0-inf_obs mg/ml*h^2 78.70742296
MRT 0-inf_obs h 3.553550208
Vz_obs (mg)/(mg/ml) 32.5371646
Cl_obs (mg)/(mg/ml)/h 9.02977146
Vss_obs (mg)/(mg/ml) 32.08774625
PKSolver 2.0 Compartmental Analysis of Plasma Data after Intravenous Bolus Input

Time Unit h
Conc Unit mg/ml Analyst Penori
Dose 200 Date 2018-5-9
Dose Unit mg Time 14:54:34

Time Conc ln(Conc) Conc_pre Residual Weight Parameter Unit

0.5 5.31 1.66959184 5.30782008 0.00217992 1 C0 mg/ml
1 4.62 1.53039471 4.62024203 -0.000242 1 k10 1/h
1.5 4.02 1.3912819 4.02173323 -0.0017332 1
2 3.5 1.25276297 3.5007556 -0.0007556 1 Parameter Unit
3 2.65 0.97455964 2.65252117 -0.0025212 1 t1/2 h
4 2.01 0.69813472 2.00981427 0.00018573 1 V (mg)/(mg/ml)
6 1.16 0.14842001 1.15385187 0.00614813 1 CL (mg)/(mg/ml)/h
8 0.66 -0.4155154 0.6624364 -0.0024364 1 AUC 0-t mg/ml*h
AUC 0-inf mg/ml*h
AUMC mg/ml*h^2
MRT h
6 Vss mg/(mg/ml)

Predicted Diagnostics Value

5 Observed r obs-pre 0.9999984878
SS 0.000058512
WSS 0.000058512
Concentration (mg/ml)

4
R^2 0.9999993556
WR^2 0.9999993556
3 SE 0.0031228198
AIC -73.970226663
SC -73.811343579
2

0
0 1 2 3 4 5 6 7 8 9
Time (h)

10

Predicted
Observed
Concentration (mg/ml)

0.1
 1

Concentrati

0.1
0 1 2 3 4 5 6 7 8 9
Time (h)

Residual Plot
0.007

0.006

0.005

0.004
Residual (mg/ml)

0.003

0.002

0.001

0
0 1 2 3 4 5 6 7 8 9
-0.001

-0.002

-0.003
Time (h)
 Value Time Conc_Pre
6.097722551 0.5 5.30782008
0.277468259 0.57575758 5.19741246
0.65151515 5.08930142
Value 0.72727273 4.98343918
2.498113421 0.8030303 4.87977899
32.79913088 0.87878788 4.77827502
9.100717725 0.95454545 4.67888243
19.58885739 1.03030303 4.5815573
21.97628869 1.10606061 4.48625662
79.20289264 1.18181818 4.39293828
3.604015844 1.25757576 4.30156106
32.79913088 1.33333333 4.21208456
1.40909091 4.12446927
1.48484848 4.03867645
1.56060606 3.9546682
1.63636364 3.8724074
1.71212121 3.7918577
1.78787879 3.71298352
1.86363636 3.63574998
1.93939394 3.56012298
2.01515152 3.4860691
2.09090909 3.4135556
2.16666667 3.34255045
2.24242424 3.27302227
2.31818182 3.20494035
2.39393939 3.13827459
2.46969697 3.07299554
2.54545455 3.00907436
2.62121212 2.9464828
2.6969697 2.8851932
2.77272727 2.82517848
2.84848485 2.76641212
2.92424242 2.70886816
3 2.65252117
3.07575758 2.59734625
3.15151515 2.54331902
3.22727273 2.4904156
3.3030303 2.43861263
3.37878788 2.38788721
3.45454545 2.33821692
3.53030303 2.28957982
3.60606061 2.24195442
3.68181818 2.19531967
3.75757576 2.14965496
3.83333333 2.10494013
3.90909091 2.06115541
3.98484848 2.01828145
4.06060606 1.9762993
4.13636364 1.93519043
4.21212121 1.89493666
4.28787879 1.8555202
4.36363636 1.81692365
4.43939394 1.77912993
4.51515152 1.74212237
4.59090909 1.70588459
4.66666667 1.6704006
4.74242424 1.6356547
4.81818182 1.60163155
4.89393939 1.56831612
4.96969697 1.53569368
5.04545455 1.50374981
5.12121212 1.47247041
5.1969697 1.44184165
5.27272727 1.41184999
5.34848485 1.38248219
5.42424242 1.35372527
5.5 1.32556652
5.57575758 1.29799349
5.65151515 1.27099401
5.72727273 1.24455615
5.8030303 1.21866822
5.87878788 1.19331878
5.95454545 1.16849663
6.03030303 1.14419081
6.10606061 1.12039057
6.18181818 1.0970854
6.25757576 1.07426499
6.33333333 1.05191928
6.40909091 1.03003837
6.48484848 1.00861261
6.56060606 0.98763252
6.63636364 0.96708884
6.71212121 0.94697249
6.78787879 0.92727458
6.86363636 0.9079864
6.93939394 0.88909943
7.01515152 0.87060533
7.09090909 0.85249593
7.16666667 0.83476321
7.24242424 0.81739936
7.31818182 0.80039669
7.39393939 0.78374769
7.46969697 0.767445
7.54545455 0.75148143
7.62121212 0.73584991
7.6969697 0.72054354
7.77272727 0.70555557
7.84848485 0.69087935
7.92424242 0.67650841
8 0.6624364
PKSolver 2.0 Compartmental Analysis of Plasma Data after Intravenous Bolus Input

Time Unit h
Conc Unit mg/ml Analyst Penori
Dose 200 Date 2018-5-9
Dose Unit mg Time 14:55:49

Time Conc ln(Conc) Conc_pre Residual Weight Parameter Unit

0.5 5.31 1.66959184 5.30784871 0.00215129 1 A mg/ml
1 4.62 1.53039471 4.62023901 -0.000239 1 Alpha 1/h
1.5 4.02 1.3912819 4.02171278 -0.0017128 1 B mg/ml
2 3.5 1.25276297 3.50072795 -0.000728 1 Beta 1/h
3 2.65 0.97455964 2.65249816 -0.0024982 1
4 2.01 0.69813472 2.00980826 0.00019174 1 Parameter Unit
6 1.16 0.14842001 1.15388393 0.00611607 1 k10 1/h
8 0.66 -0.4155154 0.66249233 -0.0024923 1 k12 1/h
k21 1/h
t1/2Alpha h
t1/2Beta h
6
C0 mg/ml
Predicted V (mg)/(mg/ml)
5 CL (mg)/(mg/ml)/h
Observed
V2 (mg)/(mg/ml)
CL2 (mg)/(mg/ml)/h
AUC 0-t mg/ml*h
Concentration (mg/ml)

4
AUC 0-inf mg/ml*h
AUMC mg/ml*h^2
3 MRT h
Vss mg/(mg/ml)
2
Diagnostics Value
r obs-pre 0.9999984988
1 SS 5.8044266E-05
WSS 5.8044266E-05
R^2 0.9999993607
0 WR^2 0.9999993607
0 1 2 3 4 5 6 7 8 9 SE 0.0038093394
Time (h) AIC -70.034437061
SC -69.716670895
10

Predicted
Observed
Concentration (mg/ml)

0.1
 1

Concentrati

0.1
0 1 2 3 4 5 6 7 8 9
Time (h)

Residual Plot
0.007

0.006

0.005

0.004
Residual (mg/ml)

0.003

0.002

0.001

0
0 1 2 3 4 5 6 7 8 9
-0.001

-0.002

-0.003
Time (h)
 Value Time Conc_Pre
3.0327845464 0.5 5.30784871
0.2800417608 0.57575758 5.19743519
3.0650176324 0.65151515 5.08931867
0.2749555336 0.72727273 4.98345137
0.8030303 4.87978648
Value 0.87878788 4.77827819
0.2774618999 0.95454545 4.67888163
2.330438E-05 1.03030303 4.58155286
0.2775120901 1.10606061 4.48624886
2.4751564861 1.18181818 4.39292751
2.5209428282 1.25757576 4.30154756
6.0978021788 1.33333333 4.21206861
32.798702571 1.40909091 4.12445112
9.1003903291 1.48484848 4.03865636
0.0027543062 1.56060606 3.9546464
0.0007643533 1.63636364 3.87238412
19.588946709 1.71212121 3.79183315
21.977079308 1.78787879 3.71295789
79.214208749 1.86363636 3.63572347
3.6044010961 1.93939394 3.56009577
32.801456877 2.01515152 3.48604135
2.09090909 3.41352748
2.16666667 3.34252211
2.24242424 3.27299386
2.31818182 3.20491199
2.39393939 3.13824641
2.46969697 3.07296767
2.54545455 3.0090469
2.62121212 2.94645586
2.6969697 2.88516687
2.77272727 2.82515286
2.84848485 2.7663873
2.92424242 2.70884421
3 2.65249816
3.07575758 2.59732424
3.15151515 2.54329808
3.22727273 2.4903958
3.3030303 2.43859401
3.37878788 2.38786981
3.45454545 2.3382008
3.53030303 2.28956501
3.60606061 2.24194096
3.68181818 2.19530759
3.75757576 2.1496443
3.83333333 2.1049309
3.90909091 2.06114763
3.98484848 2.01827514
4.06060606 1.97629449
4.13636364 1.93518711
4.21212121 1.89493485
4.28787879 1.85551992
4.36363636 1.81692489
4.43939394 1.7791327
4.51515152 1.74212666
4.59090909 1.70589041
4.66666667 1.67040794
4.74242424 1.63566356
4.81818182 1.60164192
4.89393939 1.56832799
4.96969697 1.53570704
5.04545455 1.50376465
5.12121212 1.47248672
5.1969697 1.44185941
5.27272727 1.41186919
5.34848485 1.38250282
5.42424242 1.3537473
5.5 1.32558993
5.57575758 1.29801828
5.65151515 1.27102015
5.72727273 1.24458361
5.8030303 1.21869698
5.87878788 1.19334883
5.95454545 1.16852794
6.03030303 1.14422336
6.10606061 1.12042433
6.18181818 1.09712035
6.25757576 1.07430112
6.33333333 1.05195654
6.40909091 1.03007676
6.48484848 1.00865209
6.56060606 0.98767307
6.63636364 0.96713043
6.71212121 0.94701509
6.78787879 0.92731817
6.86363636 0.90803095
6.93939394 0.88914492
7.01515152 0.87065173
7.09090909 0.85254321
7.16666667 0.83481136
7.24242424 0.81744834
7.31818182 0.80044648
7.39393939 0.78379826
7.46969697 0.76749633
7.54545455 0.75153349
7.62121212 0.73590268
7.6969697 0.72059699
7.77272727 0.70560967
7.84848485 0.69093408
7.92424242 0.67656375
8 0.66249233
0.5 2.75 0.5 5.31
1 6.24 1 4.62
1.5 8.5 1.5 4.02
2 9.81 2 3.5
3 7.43 3 2.65
4 5.6 4 2.01
6 3.19 6 1.16
8 1.91 8 0.66