Appendix:
Table 1. Summary of population PK parameters for anticonvulsants.
CLASS: ANTICONVULSANTS
Reference
Model N
Obs.
Drug
Punyawudho
et al.(1)
Deleu et
al.(2)
Jiao et al.(3)
Carbamazepine
1
121 555
Population
characteristics
θCL
(L/h)
CV
%
θV (L)
CV
%
θka
(h-1)
Elderly patients
with epilepsy
Adult Omani
epileptic patients
Chinese epileptic
patients
Epileptic patients
of Singapore
population
(majority Chinese
origin)
3.6
18.1
102
74.7
0.2
0.05a
20.0
2.2b
15.0
15.9
1.9
10.0
0.09a
21.4
0.04a
20.0
1
48
149
1
585
687
Chan et
al.(4)
1
193
302
Drug
Kelley et
al.(5)
Drug
Ouellet et
al.(6)
Felbamate
1
40
76
Children patients
Gabapentin
1
253
740
Healthy or
epileptic infants
and children
Drug
Chan et
al.(7)
Grasela et
al.(8)
Punyawudho
et al.(9)
Hussein &
Posner(10)
Lamotrigine
1
129
629
Epileptic patients
1
527
1
148
1
163
0.9b
29.7
30.6
1.2
43.0
77.5
2.1
38.0
78.1
7.0
2407 Epileptic patients
0.06a
32.2
132
44.3
1.3
875
2.6
34.2
115
2.3
32.1
77.4
33.6
3.2
Elderly patients
with epilepsy
Newly diagnosed
epileptic patients
CV
%
θQ(L
/h)
CV
%
θVp (L)
CV%
Rivas et
al.(11)
1
Drug
Pigeolet et
al.(12)
Levetiracetam
1
524 5408 Healthy or
epileptic Japanese
and western
adults
1
228 2319 Epileptic children
and adolescents
patients
Phenobarbital
1
35
69
Japanese neonates
and infants
1
70
109 Japanese neonates
and infants
Phenytoin
1
83
Neonates and
infants with
seizures
Pregabalin
1
616 5275 Healthy adult
subjects or adult
patients with
post-herpetic
neuralgia or
diabetic
peripheral
neuropathy
Tiagabine
1
511 2147 Adult patients
with epilepsy
Toublanc et
al.(13)
Drug
Yukawa et
al.(14)
Yukawa et
al.(15)
Drug
Al Za’abi et
al.(16)
Drug
Shoji et
al.(17)
Drug
Samara et
al.(18)
600
on lamotrigine
monotherapy
1699 Spanish and
German epileptic
patients
0.03a
27.5
4.0
19.5
52.7
11.8
2.2
19.0
21.5
19.0
0.02
31.9
1.1b
53.9
0.02
26.0
1.0b
61.2
0.8
74.2
74.2
65.6
0.05
14.8
35.6
8.5
20.4
4.0
28.0
4.8c
108.0c
2.4d
108.0d
1.5
100.0
8.0
93.2
Ingwersen et
al.(19)
Drug
BouillonPichault et
al.(20)
1
130
593
Drug
Park et
al.(21)
Valproic acid
1
102
354
Jiang et
al.(22)
Correa et
al.(23)
Birnbaum et
al.(24)
1
317
624
1
110
119
1
146
405
Serrano et
al.(25)
1
255
770
Topiramate
1
22
Newly diagnosed
epileptic patients
6.1
21.4
52.0
51.3
1.3
105.0
Infants and young
children with
pharmacoresistant
epilepsy
0.6e
13.0
28.6
0.2
1.0
124.0
Korean adult
patients with
epilepsy
Chinese children
with epilepsy
Mexican epileptic
paediatric patients
Nursing home
epileptic elderly
patients
Children patients
with epilepsy
0.8
32.0
15.1
18.0
0.1
25.1
2.9
49.1
0.3
11.0
0.04
14.1
0.8
32.9
1.2f
21.4
a: units of L/h/kg; b: units of L/kg; c: for fasting state; d: for fed state; e: without concomitant use of enzyme-inducing anticonvulsants; f: with
concomitant use of enzyme-inducing anticonvulsants
Table 2. Significant covariates for CL of anticonvulsants.
CLASS: ANTICONVULSANTS
Covariates
Drugs
Carbamazepine(3), felbamate(5), phenobarbital(14),(15), phenytoin(16), valproate acid(22),(23),(25)
Age
Lamotrigine(10)
Auto-induction
Lamotrigine(9)
Blood urea
nitrogen/serum
creatinine ratio
Co-medications
Dose
Formulation
Height
Race
Renal function
Serum concentration
Sex
Weight
Carbamazepine(1),(3),(4), felbamate(5), lamotrigine(7),(8),(9),(11), levetiracetam(12),(13), tiagabine(18),
topiramate(20), valproic acid(22),(23),(24),(25)
Carbamazepine(3), 4alproic acid(23),(25)
Valproic acid(24)
Tiagabine(19)
Gabapentin(6), lamotrigine(8),(10),
Gabapentin(6), levetiracetam(12),(13), pregabalin(17),
Phenobarbital(15)
Levetiracetam(12), valproaic acid(24)
Carbamazepine(3),(4), lamotrigine(9),(11), levetiracetam(12),(13), phenobarbital(14),(15), phenytoin(16),
4alproic acid(21),(23),(25)
Table 3. Significant covariates for V of anticonvulsants.
CLASS: ANTICONVULSANTS
Covariates
Drugs
Topiramate(20)
Age
Levetiracetam(12)
Co-medications
Levetiracetam(12)
Comorbidities
Lamotrigine(8)
Gender
Tiagabine(19)
Height
Gabapentin(6), levetiracetam(12),(13), phenobarbital(14),(15), phenytoin(16), pregabalin(17), topiramate(20),
Weight
4alproic acid(21),(22)
Table 4. Summary of population PK parameters for antipsychotics.
CLASS: ANTIPSYCHOTICS
Reference
Model N
Obs.
Drug
Kim et
Aripiprazole
1
80
141
Population
characteristics
θCL
(L/h)
CV
%
θV (L)
CV
%
Korean adult
3.2a
30.5
193
31.6
θka
(h-1)
CV
%
θQ(L
/h)
CV
%
θVp (L)
CV%
al.(26)
psychiatric
patients
Drug
Dailly et
al.(27)
Clozapine
1
23
Ismail et
al.(28)
1
391
Ng et al.(29)
1
197
519
Adult psychiatric
patients
Drug
Yukawa et
al.(30)
Drug
Bigos et
al.(31)
Haloperidol
1
218
391
Japanese adult
patients
Lobo et
al.(32)
1
Drug
Samtani et
al.(33)
Drug
Jin et al.(34)
Paliperidone
1
1795 18530 Adult psychiatric
patients
Perphenazine
1
156 421 Adult
schizophrenic
patients
Risperidone
1
490 1236 Adult patients
Drug
Feng et
Olanzapine
1
523
116
83
Adult
schizophrenic
patients
1142 Schizophrenic
patients
1527 Adult patients
with Alzheimer’s
disease or
schizophrenia
462 Adolescent
patients with
schizophrenia or
bipolar I disorder
2.7b
2.3c
1.8d
32.3
27.1
272
22.5
36.7e
27.0f
18.0g
24.0h
44.5
93.2
60.8
131.5 0.1i
10.3j
42.4
30.3
34.4k
46.8
16.1
68.0
2150
86.0
13.6
40.5
899
65.4
5.0
40.0
391
69.0
512g,l
346g,m
159h
79.3
19300
78.5
336.1
12.9n
95.9
444
36.1
53.7
0.5
59.0
with Alzheimer’s
disease or
schizophrenia
al.(35)
Thyssen et
al.(36)
2
780
Vermeulen et 2
al.(37)
407
Drug
Wessels et
al.(38)
Ziprasidone
1
233
3436 Healthy adults or
children,
adolescents and
adults with
psychiatric
5359 Adult patients
with
schizophrenia or
bipolar disorder
568
Schizophrenic
patients
65.4o
56.6
13.7
142
2.8
184.0 137
30.0
122
64.8
104.4
1060
2.3
3.2
175
39.9
149.0 3.7
215.0 100
53.9
a: for patients with 2 functional alleles of CYP2D6; b: for patients with 1 partially deficient allele and 1 functional allele of CYP2D6; c: for patients with
1 null allele and 1 functional allele of CYP2D6; d: for patients with no functional allele of CYP2D6; e: for male patients; f: for female patients; g: for
non-smokers; h: for smokers; i: for tablet form; j: for suspension; k: units of L/kg; l: for African Americans; m: for non-African Americans; n: for
CYP2D6 poor metabolisers; o: for CYP2D6 extensive metabolisers
Table 5. Significant covariates for CL of antipsychotics.
CLASS: ANTIPSYCHOTICS
Covariates
Drugs
Clozapine(28), haloperidol(30)
Age
Haloperidol(30), risperidone(37)
Co-medications
Haloperidol(30)
Dose
Olanzapine(31), perphenazine (34)
Ethnicity
Aripiprazole(26), clozapine(27)
Genetic polymorphism
Paliperidone(33)
Liver function
Clozapine(28),(29), olanzapine(31),(32), paliperidone(33)
Sex
Clozapine(29), olanzapine(31), perphenazine(34)
Risperidone(37)
Haloperidol(30), olanzapine(32)
Smoking
Study
Weight
Table 6. Significant covariates for V of antipsychotics.
CLASS: ANTIPSYCHOTICS
Covariates
Drugs
Haloperidol(30)
Age
Paliperidone(33)
Body mass index
Paliperidone(33)
Sex
Table 7. Summary of population PK parameters for antidepressants.
CLASS: ANTIDEPRESSANTS
Reference
Model N
Obs.
Drug
Bies et
al.(39)
Citalopram
1
106
Yin et al.(40)
1
Drug
MeyerBarner et
al.(41)
Drug
Lobo et
al.(42)
Doxepin
1
114
199
53
Duloxetine
1
594
383
Population
characteristics
θCL
(L/h)
CV
%
θV (L)
CV
%
Adult patients with
bipolar depression
or major
depressive disorder
Chinese adult
patients with
mood or anxiety
disorder
10.2
57.7
157
279.0 0.009
20.8a
17.0b
12.7c
23.4
641.9a 103.4
631.2b
736.1c
Patients with
major depression
102.4
59.0
2292.4 179.0
58.9
814
2002 Adult patients with 45.1
major depressive
96.6
θka
(h-1)
0.2
CV
%
45.1
θQ(L
/h)
CV
%
θVp (L)
CV%
disorder, diabetic
peripheral
neuropathic pain,
stress UI or
fibromyalgia
Drug
Jin et al.(43)
Escitalopram
1
172
473
Adult patients
with major
depressive
disorder
26.0d
48.5
947
62.0
37.4
20.5
0.8
78.9
19.8e
Drug
Wilens et
al.(44)
Fluoxetine
1
21
168
Paediatric patients 0.2
with major
depressive
disorder
52.0
Drug
Grasmader et
al.(45)
Mirtazapine
1
65
324
Patients with
depression
32.9
1319.2
a: for CYP2C19 homozygous extensive metabolisers; b: for CYP2C19 heterozygous extensive metabolisers; c: for CYP2C19 poor metabolisers; d: for
CYP2C19 extensive metabolisers; e: for CYP2C19 both intermediate and poor metabolisers.
Table 8. Significant covariates for CL of antidepressants.
CLASS: ANTIDEPRESSANTS
Covariates
Drugs
Citalopram(39), doxepin(41), duloxetine(42), escitalopram(43), fluoxetine(44)
Age
Fluoxetine(44)
Body mass index
Doxepin(41)
Co-medication
Duloxetine(42)
Dose
Citalopram(40), escitalopram(43), mirtazapine(45)
Genetic polymorphism
Duloxetine(42)
Sex
Duloxetine(42)
Smoking
Citalopram (39),(40), escitalopram(43), fluoxetine (44)
Weight
Table 9. Significant covariates for V of antidepressants.
CLASS: ANTIDEPRESSANTS
Covariates
Drugs
Citalopram(39), fluoxetine(44)
Age
Escitalopram(43), fluoxetine(44)
Body mass index
Duloxetine(42)
Ethnicity
Citalopram(39), doxepin(41), fluoxetine(44)
Weight
Table 10. Summary of population PK parameters for other psychotropics.
CLASS: OTHER PSYCHOTROPICS
Reference
Model N
Obs. Population
characteristics
Levodopa
Drug
Jorga et
1
296 1401 Adult patients
al.(46)
with Parkinson’s
disease
(fluctuator)
1
97
544 Adult patients
with Parkinson’s
disease (nonfluctuator)
Lithium
Drug
Yukawa et
1
90
303 Patients treated
al.(47)
with lithium
Midazolam
Drug
Ahsman et
2
20
293 Neonates sedated
al.(48)
during ECMO
Burtin et
2
187 531 Neonates sedated
al.(49)
for artificial
ventilation
θCL
(L/h)
CV
%
θV (L)
CV
%
18.1a
26.0
99.2
42.0
33.0
124
80.0
θka
(h-1)
CV
%
θQ(L
/h)
CV
%
θVp (L)
CV%
28.5b
17.0a
24.9b
25.1
0.2c
85.6
0.07c
65.0
0.6d
87.0
0.2c
4.4d
85.0
0.3
0.4
96.0
Peeters et
al.(50)
2
24
Drug
Jorga et
al.(51)
Tolcapone
2
215
981
2
433
60
Sedation of non9.4
ventilated
children after
major craniofacial
surgery
54.0
3.8
18.0
30.2
82.0
Adult patients
with Parkinson’s
disease
(fluctuator)
Adult patients
with Parkinson’s
disease (nonfluctuator)
4.8
29.0
16.0
72.0
1.7
5.2
12.0
57.0
4.5
25.0
3.5
168.0 0.7
7.7
24.0
a: levodopa dose taken with benserazide (Madopar); b: levodopa dose taken with carbidopa (Sinemet); c: units of L/h/kg; d: units of L/kg
Table 11. Significant covariates for CL of other psychotropics.
CLASS: OTHER PSYCHOTROPICS
Covariates
Drugs
Lithium(47)
Age
Midazolam(52)
Body surface area
Midazolam(49)
Co-medications
Levodopa(46)
Dose
Midazolam(49)
Gestational age
Levodopa (46), lithium(47)
Renal function
Levodopa(46)
Sex
Midazolam(48)
Time after cannulation
Lithium(47), midazolam(48)
Weight
Table 12. Significant covariates for V of other psychotropics.
CLASS: OTHER PSYCHOTROPICS
Covariates
Drugs
Midazolam(52)
Body surface area
Levodopa(46)
Sex
Midazolam(48)
Time after cannulation
Levodopa(46), midazolam(48)
Weight
Table 13. Summary of population PK parameters for immunosuppressants.
CLASS: IMMUNOSUPPRESSANTS
Reference
Model N
Obs. Population
characteristics
Alemtuzumab
Drug
Mould et
2
67
1565 Patients with CLL
al.(53)
Basiliximab
Drug
Kovarik et
2
169 1418 Adult renal
al.(54)
transplant patients
Kovarik et
2
188 1533 Adult liver
al.(55)
transplant patients
Cetuximab
Drug
Dirks et
2
143 912 Patients with
al.(56)
squamous cell
carcinoma of the
head and neck
Ciclesonide
Drug
Xu et al.(57) 2
32
288 Patients with
persistent asthma
Rohatagi et
al.(58)
Drug
Rosenbaum
et al.(59)
1
Wu et al.(60)
1
151
Cyclosporin
1
48
120
θCL
(L/h)
CV
%
θV (L)
CV
%
11.3
84.0
θka
(h-1)
CV
%
θQ(L
/h)
θVp (L)
CV%
1.1
41.5
179.0
CV
%
0.037
41.4
8.0
0.055
47.7
5.7
15.7
2.83
18.6
2.43
56.4
0.103 97.2
2.43
56.4
120.4 196.0 59.8
652c
995d
30.3
202.0a
271.0b
3300 Asthmatic patients 396.0
46.9
947
70.0
2.63
64.8
1190
41.2
4.42e
1004 Adult cardiopulmonary
transplant
recipients
2548 Adult renal
23.1
32.1
202
28.5
19.7
133
1.28
179.0
transplant
recipients
Drug
Pescovitz et
al.(61)
Daclizumab
2
61
Drug
Nakade et
al.(62)
Drug
Sun et al.(63)
Dexamethasone
1
440 847
Mortensen et
al.(64)
1
Drug
Yim et
al.(65)
Etanercept
1
69
Lee et al.(66)
1
Drug
Kovarik et
al.(67)
Moes et
al.(68)
Drug
Xu et al.(57)
Drug
Everolimus
1
673
Efalizumab
1
1088
70
102
Paediatric patient
with renal
transplant
5.24f
Patients with
cancer
13.3
30.0
10.8g
14.5h
0.92f
40.0
0.006
1.69g
2.49h
86.1
22.6
Adults with
0.05
48.2 9.13
psoriasis
Adults with plaque 0.001i,j 76.0psoriasis
80.0
0.0006i,k
28.6
0.008
40.2
1102 Paediatric patients 0.0576d
with juvenile RA
0.0772c
29.0
7.88
87.0
0.05
215.0
4284 Adult RA patients 0.117d
0.138c
41.1
16.1
41.7
0.332
24.3
5260 Renal transplant
patients
2
53
136 Adult renal
17.9
transplant patients
Fluticasone Propionate
1
32
288 Asthmatic patients 890.0
Golimumab
1.36
27.0
36.0
26.2
148
27.7
7.55
108.6 55.7
57.2
9800
61.8
4.07
66.2
498
Xu et al.(69)
1
337
Zhou et
al.(70)
Drug
Xu et al.(71)
2
26
Fasanmade
et al.(72)
Ternant et
al.(73)
2
482
2
33
Drug
Dartois et
al.(74)
Drug
Kuester et
al.(75)
Inolimomab
2
21
Drug
Min et
al.(76)
Methotrexate
2
82
Colom et
al.(77)
Fukuhara et
al.(78)
1
14
2
51
Infliximab
2
274
Matuzumab
2
90
2029 Patients with
0.575
psoriatic arthritis
198 Adult RA patients 0.0167
37.6
24.9
37.9
44.6
3.07
25.5
0.018 44.6
3.68
1096 Patients with
ankylosing
spondylitis
4145 Patients with
ulcerative colitis
478 Patients with
Crohn’s disease or
ulcerative colitis
0.011
34.1
3.06
17.5
0.072
2.94
0.017
37.7
3.29
22.1
4.13
0.3
0.032l
0.032m
22.5l 2.3c
27.4m 1.1d
14.1c
11.3d
0.005 10.0
1.9
318
Patients with
acute GvHD
0.077
43.0
2.76
68.0
2.22
2.25
1256 Patients with
advanced
carcinoma
0.146
31.9
3.73
24.4
0.362
50.6
25.9
22.5
0.33
3
400
Patients with
7.45
lymphoid
malignancy
1304 Paediatric patients
with osteosarcoma
348n Japanese cancer
416o patients
11.9
8.9
26.4p 26.9
41.9q
32.1
0.07
8
43.0
70.4
44.6
15.0
1.8
59.8
9.23
97.8
2.27
Yukawa et
al.(79)
2
34
Godfrey et
al.(80)
2
62
Drug
Ishida et
al.(81)
Drug
Staatz et
al.(82)
Payen et
al.(83)
Mizoribine
1
114
Guillet et
al.(84)
Zhao et
al.(85)
Zeng et
al.(86)
Sam et
al.(87)
de Winter et
al.(88)
van Hest et
Japanese patients
with rheumatoid
arthritis
3260 Patients with
rheumatoid
arthritis
25.7
0.05r
217.9 0.503
27.2
25.2
27.9
1.88s
2.75t
76.7s 3.22
44.0t
41.1
0.858r
50.9
0.983
101.5
34.9u
25.4v
17.2
32.0
65.0
0.64
109.0 30.7
0.027i,w
51.0
47.6
31.0
33.1
15.0
53.5
33.2
61.6
18.6
6.4
31.6
7.24
10.6
21.4
25.9
87.8
16.0
39.0
40.0
100.0 4.1e
187.0 22.0
33.0
31.0
91.0
91.0
4.1e
111.0 35.0
153
449
6.05
Adult renal
transplant patients
Mycophenolic Acid
2
117 1376 Adult renal
transplant patients
2
32
449 Paediatric and
adolescent renal
transplant patients
2
20
486 Adult kidney
transplant patients
with chronic graft
dysfunction
2
89
497 Paediatric renal
transplant patients
2
38
859 Children and
young people with
blood marrow and
solid organ
transplantation
2
18
232 Renal transplant
patients
2
259 3764 Renal transplant
patients
2
140 6523 Renal transplant
0.056i 22.3
0.368r
40.5
25.7
78.0
496.0
31.2
51.0
724
128.0
0.233i,x
0.39
0.673
59.1
115.3 183.0
3.74
16.8
8.11
39.6
239.0
518.0
490.0
237.0
102.0
78.0
al.(89)
Le Guellec et 2
60
al.(90)
Omalizumab
Drug
Hayashi et
1
202
al.(91)
Drug
Ma et al.(92)
Drug
Ng et al.(93)
Drug
Petersen et
al.(94)
Drug
Call et
al.(95)
Drug
Ng et al.(96)
Drug
300
patients
Stable renal
0.246i
transplant patients
3192 Asthmatic
patients
0.0073
Panitumumab
2
1200 8482 Patients with
0.0113
advanced solid
tumours
Pertuzumab
1
153 1458 Patients with
0.0089
solid
malignancies,
ovarian cancer
and metastatic
breast cancer
Prednisolone
2
23
288 Children with
acute
lymphoblastic
leukaemia
rATG, thymoglobulin
2
13
Paediatric patients 4.53
with hematologic
malignancies
Rituximab
2
102 1002 Patients with RA
Sibrotuzumab
0.0001
29.2
36.0
63.1
20.3
5.9aa
13.0aa 0.02
3.63ab
25.0ab
28.0
3.95
34.0
0.016
2.59
31.1
2.74
16.2
0.027
3.64
14.0
50.0
61.0
28.2
2.98
12.3
25.9
44.7
137.0
39.9
38.0
42.0
Kloft et
al.(97)
Drug
Ferron et
al.(98)
Jiao et
al.(99)
2
60
1844 Cancer patients
0.022
57.0
4.13
20.0
Sirolimus
2
36
636
8.91
38.2
112.9
31.8
1
112
804
10.1
23.8
3670
56.7
Djebli et
al.(100)
Drug
Eriksson et
al.(101)
Drug
Fukudo et
al.(102)
Zahir et
al.(103)
2
22
938
Renal transplant
patients
Chinese adult
renal transplant
patients
Renal transplant
patients
15.9
58.1
218.0
52.7
Multiple
myeloma patients
8.98
63.8
19.0
53.9
48.7
31.6
20.0r
17.1r
314.0
74.0
82.6
Zhao et
al.(104)
Benkali et
al.(105)
Wallin et
al.(106)
1
50
41.9
28.5
132.0 0.462
1
41
486
53.0
1
22
3.71r
122.0
Antignac et
al.(107)
Li et al.(108)
1
83
98.4
79.0
4.5
1
104
217
36.6
2.08
Thalidomide
1
40
Tacrolimus
2
100
30
1
67
381
3054 Paediatric liver
0.165i
1005 transplant patients 0.134i
690 Adult liver
21.3
transplant
recipients
289 Paediatric renal
18.5
transplant patients
Adult renal
transplant patients
743 Paediatric
0.106ac
hematopoietic
stem cell
transplant patients
1589 Renal transplant
patients
1106 Adult liver
14.1
transplant patients
50.0
13.7
0.032
2.18
0.2
41.3
3.19
20.0
25.2
31.9
452.0
26.4
38.2
75.0
273
11.5
48.3
89.9
276
16.0
4.5
76.2
14.0
Sam et
al.(109)
Antignac et
al.(110)
Fukatsu et al.
(111)
Sam et
al.(112)
1
1
31
29
37
213
157
728
Asian liver
transplant patients
Adult liver
transplant patients
824 Patients with liver
transplant
771 Asian paediatric
liver transplant
patients
1060 Adult kidney
transplant
recipients
3284 Pediatric liver
transplant
recipients
1
35
1
16
Staatz et
al.(113)
1
70
Wallin et
al.(114)
1
73
Drug
Frey et
al.(115)
Drug
Zhu et
al.(116)
Tocilizumab
2
1793 7415 Adult RA patients 0.0003
Utsekinumab
1
1937 9938 Patients with
moderate to
severe plaque
psoriasis
537
23.8
563
25.9
36.0ad
43.0
1870
49.0
57.4
1.52r
39.7
1.46
33.5
39.1
33.0
33.5
42.0
898
11.0
0.0014i,ae 65.0ae 27.2
90.0
5.21
6.5
4.48
0.0015i,af
0.0194
54.0
3.5
37.0
39.5
15.7
33.8
0.008
2.9
66.0
0.015
a: non-ciclosenide treatment period; b: ciclesonide treatment period; c: male; d: female; e: fixed ; f: less than 5 years old; g: 6-12 years old; h: 13-17years old;
i: unit of L/h/kg; j: dose given 1.0mg/kg/week; k: dose given 2.0mg/kg/week; l: antibodies towards infliximab positive; m: antibodies towards infliximab
negative; n: blood; o:urine p: renal; q: non-renal; r: units of L/kg; s: oral; t: intramuscular; u: cyclosporine co-therapy; v: 18irolimus18 co-therapy; w: day 21,
x: post 6 months; aa: free; ab: bound; ac: L/h/kg-0.75; ad: Clmax; ; ae: CL/Fmax; af: Fo:CL/F0
Table 14. Significant covariates for CL of immunosuppressants.
CLASS: IMMUNOSUPPRESSANTS
Covariates
References
Basiliximab(55), 19irolimus19ic(60), dexamethasone (62), efalizumab (63), 19irolimus19 (67), methotrexate
Age
(77), (80), 19irolimus19(104),(107),(112),(114)
Infliximab.(72), (73)
Antibodies
Antibody to drug status Golimumab(69), infliximab(71)
Etanercept(65), rituximab(96), predinisolone(94), tocilizumab(115),
Body surface area
Cyclosporin(117),(59),(60), dexamethasone(62), 19irolimus19ic acid(82),(86), 19irolimus(99),
Co-medications
19irolimus19(107)
Cyclosporin(59)
Co-morbidities
Golimumab(69)
C-reactive protein level
Methotrexate(77),(78),(80), 19irolimus19ic acid(118),(86),(89)
Creatinine clearance
Mycophenolic acid(89), utsekinumab(116)
Diabetes
Efalizumab(63), tocilizumab(115)
Disease severity
Methotrexate(78), sibrotuzumab(99)
Drug dose
Ciclesonide(57)
Drug exposure
Cyclosporin(117), 19irolimus19(113)
Duration of therapy
Daclizumb(61), dexamethasone(62), etanercept(66)
Ethnicity
Sirolimus(100), 19irolimus19(102),(104),(105),(108)
Genetic polymorphism
Tacrolimus(111)
Grafted hepatic weight
Cyclosporin(117),(60), 19irolimus19(103),(104),(113)
Haematocrit level
Tacrolimus(104)
Haemoglobin level
Etanercept(65)
Health condition
Cetuximab(56)
Ideal body weight
Utsekinumab(116)
Immune response
Sibrotuzumab(99)
Initial drug
concentration
Sibrotuzumab(99), tocilizumab(115)
Lipids
Liver enzymes
Liver function
Multiple dosing
Obesity
Postoperative days
Proteinaemia
Red blood cell count
Renal function
Serum albumin
Serum creatinine
Sex
Smoking status
Weight
White blood cell levels
Cyclosporin(60), pertuzumab(93),(113),(114), 20irolimus20(107)
Tacrolimus(109),(111)
Methotrexate(79)
Efalizumab(63)
Cyclosporin(60), 20irolimus20(102),(104),(107),(110),(111),(114)
Tacrolimus(107)
Sibrotuzumab(99)
Tacrolimus(109)
Infliximab(72), 20irolimus20ic acid(82),(84),(118),(86),(89), pertuzumab(93), 20irolimus20(103),(113),
Methotrexate (76), (78) 20irolimus20 (106)
Etanercept(65),(66) 20irolimus20(104), methotrexate(80), 20irolimus20ic acid(89), rituximab(96),
tocilizumab(115)
Golimumab(69)
Basiliximab(55), daclizumb(61), dexamethasone(62), methotrexate(77),(79), 20irolimus20(67), golimumab(69),
matazumab(75), 20irolimus20ic acid(82),(84) (86),(89),(90), omalizumab(91), panitumumab(92),
pertuzumab(93), rATG, thymoglobulin(95), rosenbatum(59), sibrotuzumab(97) , 20irolimus20(85),(109),
utsekinumab(116),
Cetuximab(56), efalizumab(63), infliximab(71)
Table 15. Significant covariates for V of immunosuppressants.
CLASS: IMMUNOSUPPRESSANTS
Covariates
References
Basiliximab(55), methotrexate(80), 20irolimus20ic acid(85)
Age
Infliximab(71), pertuzumab(93), 20irolimus20(112)
Body surface area
Mycophenolic acid(85)
Co-medication
Methotrexate(80), 20irolimus20ic acid(89)
Creatinine clearance
Mycophenolic acid(89), utsekinumab(116)
Diabetes
Disease severity
Drug dose
Erythrocyte to plasma
concentration
Ethnicity
Fasting state
Haematocrit level
Height
Initial drug
concentration
Protein level
Serum albumin
Sex
Weight
Etanercept(65)
Mycophenolic acid(89)
Tacrolimus(109)
Daclizumab(61), 21irolimus21(67)
Methotrexate(80)
Tacrolimus(109)
Tacrolimus(109)
Sirolimus(99)
Tocilizumab(115)
Mycophenolic acid(89), tocilizumab(115)
Ciclesonide(57), infliximab(71),(73), methotrexate(80), rituximab(96)
Basiliximab(55), cetuximab(56), ciclesonide(58), daclizumab(61), etanercept(65), 21irolimus21(67),
golimumab(69),(70), infliximab(72),(73), matuzumab(75), methotrexate(76),(77),(80), 21irolimus21ic
acid(83),(85), omalizumab(91), panitumumab(92), prednisolone(94), sibrotuzumab(97), 21irolimus(98),
utsekinumab(116)
Table 16. Summary of population PK parameters for colony stimulating factors.
CLASS: COLONY STIMULATING FACTORS
Reference
Model N
Obs. Population
characteristics
rhG-CSF
Drug
Fukuda et
2
25
125 Adult lung cancer
al.(119)
patients
θCL
(L/h)
CV
%
θV (L)
CV
%
0.65
51.5
3.09
29.5
θka
(h-1)
CV
%
θQ(L
/h)
0.1
CV
%
θVp (L)
497
CV%
Table 17. Summary of population PK parameters for antiarrhythmics.
CLASS: ANTIARRHYTHMICS
Reference
Model N
Obs.
θCL
(L/h)
CV
%
θV (L)
CV
%
1360 Adult patients with
refractory
ventricular
tachycardia or
fibrillation
2139 Adult patients with
CHF, renal
impairment
605 Adults arrhythmic
patients
0.2a
31.0
0.3b
46.0
0.1a
41.9
0.1b
9.5
31.2
882
Digoxin
1
141
586
Adult patients with
arrhythmia
Adult patients with
congestive heart
failure
Adult patients with
heart failure and
atrial fibrillation
Adults patients
with acute atrial
fibrillation
4.87
Adult patients with
neuropathic pain
Drug
KorthBradley et
al.(120)
Amiodarone
2
245
Vadiei et
al.(121)
2
93
Pollak et
al.(122)
Drug
Sheiner et
al.(123)
Yukawa et
al.(124)
2
77
1
385
548
Yukawa et
al.(125)
2
106
246
Hornestam et
al.(126)
2
105
210
Drug
Schnider et
al.(127)
Lignocaine
2
13
291
Population
characteristics
476
3.6
22.5
0.04
29.3
1.8
9.9
66.0
27.8
0.01
24.5
34.5b
θka
(h-1)
CV
%
θQ(L
/h)
CV
%
θVp (L)
CV%
0.7a
39.0
10b
67.0
24.5
56.2
12700
58.4
0.1
37.8
22.6
64.0
21.7
444
53.4
0.03
35.4
60.6b
33.0
Drug
Vozeh et
al.(128)
Mixeletine
1
58
452
Adult patients with
congestive heart
failure and liver
function test
0.4a
42.0
5.3
40.0
Drug
Ogawa et
al.(129)
Pilsicainide
2
91
237
Adult patients with
Brugada syndrome
and atrial
fibrillation
0.05a
2.0
0.08b
10.1
Drug
Fattinger et
al.(130)
Quinidine
2
60
260
Adult patients with 0.06
supra-ventricular or
ventricular
arrhythmia
40.2
161
76.5
Drug
Laer et
al.(131)
Sotalol
1
76
608
2.1
25.9
15.8
27.0
Shi et
al.(132)
2
611
Paediatric patients
with
supraventricular
tachycardia
Paediatric patients
with supraventricular
tachycardia or
ventricular
tachycardia
3.6
21.6
24.2
20.3
59
a: units of L/h/kg; b: units of L/kg
3.1
205.0
0.03
17.5
0.8b
6.4
66.7
1.05
48.2
6.3
21.6
40.2
20.3
Table 18. Significant covariates for CL of antiarrhythmics.
CLASS: ANTIARRHYTHMICS
Covariates
Drugs
Amiodarone(120),(121),(122), digoxin(124), lignocaine(127),(133), pilsicainide(129), propofol(134),(135),
Age
sotalol(131),(132)
Sotalol(132)
Body surface area
Lignocaine(133)
Cardiac output
Amiodarone(120),(121), digoxin(123),(126), pilsicainide(129), propofol(134), quinidine(130)
Creatinine clearance
Glomerular filtration rate Sotalol(131)
Propofol(134)
Heart rate
Amiodarone(122), propofol (134), sotalol(131)
Height
Amiodarone(122)
Lean body mass
Amiodarone(122), digoxin(124),(125), lignocaine(127), pilsicainide(129), propofol (134),(135),(136),
Sex
sotalol(131)
Amiodarone(120),(121),(122), digoxin (124, 125), lignocaine(127),(133), mixeletine(128), pilsicainide(129),
Weight
propofol(134), (135),(136), quinidine(130), sotalol(131),(132)
Table 19. Significant covariates for V of antiarrhythmics.
CLASS: ANTIARRHYTHMICS
Covariates
Drugs
Amiodarone(120),(121),(122), digoxin(124), lignocaine(127),(133), pilsicainide(129), propofol(134),(135, 136),
Age
sotalol(131),(132)
Sotalol(132)
Body surface area
Lignocaine(133), sotalol(132)
Cardiac output
Amiodarone(122), propofol(134), sotalol(131)
Height
Amiodarone(122), digoxin(124), lignocaine(127), pilsicainide (129), propofol(134),(135, 136), sotalol(131)
Sex
Amiodarone(120),(121),(122), digoxin(124, 125), lignocaine(127),(133), mixeletine(128), pilsicainide(129),
Weight
propofol(134),(135),(136), quinidine(130), sotalol(131),(132)
Table 20. Summary of population PK parameters for anticoagulants.
CLASS: ANTICOAGULANTS
Reference
Model
N
Obs.
Drug
Akimoto et
al.(137)
Argatroban
2
140
Drug
Troconiz et
al.(138)
Dabigatran etexilate
2
287 4604
Liesenfeld
et al.(139)
Drug
Gibiansky
et al.(140)
2
9522
Drug
Sanchez et
al.(141)
Enoxaparin
1
556
Eltrombopag
2
199
4093
Population
characteristics
θCL
(L/h)
CV
%
θV (L)
CV
%
Patients
undergoing
elective
percutaneous
coronary
interventions
21
37.0
9.2
31.0
θka
(h-1)
Patients
43.4a
undergoing
primary elective
82.1b
hip replacement
surgery
Patients with non- 124
valvular AF
108.6a 30.8
0.022
46.0b
0.265
Patients with
0.663
chronic idiopathic
thrombocytopenic
purpura
40.6
Patients
undergoing
percutaneous
coronary
intervention
33.0
1.2
CV
%
θQ(L
/h)
29.8
CV%
6.6
43.0
345
37.4
0.497c
10.2d
2.9
θVp (L)
136
673
8.7
CV
%
30.0
0.405
11.4
20.5
Trame et
al.(142)
2
126
Hulot et
al.(143)
1
60
Bruno et
al.(144)
1
448
Sanderink
et al.(145)
1
12
Sanderink
et al.(145)
1
12
Sanderink
et al.(145)
1
Lebaudy et
al.(146)
Drug
Meuck et
al.(147)
1
189
54.0
169e
42.0
0.72
23.0
6.65
54.0
0.41
0.733
27.0
5.24
56.1
0.235
0.99f
0.87g
0.9f
37.0f
41.0g
33.0f
0.76g
32.0g
Patients with
severe renal
impairment
Pregnant women
0.73f
33.0f
0.58g
44.0g
0.81
20.3
7.1
26.0
Patients
undergoing total
hip replacement
5.46h
6.91i
7.51j
38.2
58.2
32.4
Patients with
moderate renal
impairment
12
75
Rivaroxaban
1
758
45.2e
Children and
adolescents
during secondary
thromboembolic
prophylaxis
Patients (> 60 years
and/or with renal
insufficiency) with
ACS (unstable
angina, non Q
wave MI)
Patients with
unstable angina,
non ST elevation
myocardial
infarction
Patients with mild
renal impairment
5743
10.3
0.047k
0.222l
1.071m
1.49n
Meuck et
al.(148)
1
1009 7565
Drug
Brunet et
al.(149)
UF Heparin
1
35
Drug
Lane et
al.(150)
S- Warfarin
1
306
Drug
Lane et
al.(150)
R-Warfarin
1
309
Drug
Mungall et
al.(151)
Drug
Baathe et
al.(152)
Warfarin (racemate)
1
163 613
Cullberg et
al.(153)
1
Ximelagatran
1
3355 9879
264
1836
Patients
undergoing major
orthopaedic
surgery
6.4o
70.1o 49.1
7.3p
38.6p
Long term
haemodialysis
patients
1.4
28.0
1.9
Patients
commencing
warfarin therapy
0.144
41.3
16.6
35.8
1.66
Patients
commencing
warfarin therapy
0.125
43.0
10.9
38.3
1.66
45.0
1.2
120.0
1.18
90.0
Adult patients
28.0
Patients with atrial 24.4
fibrillation
receiving long term
anticoagulant
therapy
Patients with
27.3
acute deep vein
thrombosis
27.0
211
19.0
176
a: before 24 hours; b: after 24 hours; c: ka before MTIME; d: ka after MTIME; e:parameters expressed as per kg; f: day 1 of study; g: day 4 of study; h: on
day 2 of study; i: on study days 3 -4; j=:on days >4; k: on study day 2 for population 1; l: on study days 3-4 for population 1; m: on study days< 4 for
population 2; n: on study days>4 for population 2; o: on study days <3; p: on study days > 3
Table 21. Significant covariates for CL of anticoagulants.
CLASS: ANTICOAGULANTS
Covariates
Drugs
Argatroban(138)
Fasted serum gastric
concentrations
Dabigatran etexilate(139), enoxaparin(143),(147), UF Heparin(149)
Age
Eltrombopag(140), enoxaparin(142),(143), UF heparin(150)
Body weight
Eltrombopag(140)
Concomitant
corticosteroids
Dabigatran etexilate(139), enoxaparin(143),(147)
Creatinine clearance
UF Heparin(150)
CYP2C9 genotype
Eltrombopag(140)
Dose
Dabigatran etexilate(139)., eltrombopag(140)
Ethnic subgroup
Enoxaparin(147)
Haematocrit
Dabigatran etexilate(139)
Heart Failure
Enoxaparin(143).
Serum creatinine
Dabigatran etexilate(139), eltrombopag(140), rivaroxaban(148), UF heparin(150).
Sex
Table 22. Significant covariates for V of anticoagulants.
CLASS: ANTICOAGULANTS
Covariates
Drugs
Dabigatran etexilate(139), eltrombopag(140), enoxaparin(142), rivaroxaban(148)
Body weight
Eltrombopag(140)
Dose
Dabigatran etexilate(139)
Haemoglobin
Eltrombopag(140)
Race
Table 23. Summary of population PK parameters for antiplatelets.
CLASS: ANTIPLATELETS
Reference
Model N
Obs.
Drug
Ernest II et
al.(154)
Drug
Ernest II et
al.(154)
Drug
Ernest II et
al.(154)
Population
characteristics
Clopidogrel (active metabolite)
1
54
556 Aspirin treated
patients with
coronary artery
disease
Prasugrel (active metabolite)
1
55
751 Aspirin treated
patients with
coronary artery
disease
Prasugrel (thiolactone metabolite)
1
55
763 Aspirin treated
patients with
coronary artery
disease
θCL
(L/h)
CV
%
θV (L)
CV
%
3420
42.4
470
55.3
149
33.5
66.4
33.5
36.9
28.8
60.5
28.8
Table 24. Significant covariates for CL of antiplatelets.
CLASS: ANTIPLATELETS
Covariates
Drugs
Prasugrel (active metabolite)(154)
Body weight
Prasugrel (active metabolite)(154)
Dose
Prasugrel (active metabolite)(154)
Sex
θka
(h-1)
CV
%
θQ(L
/h)
CV
%
θVp (L)
CV%
Table 25. Summary of population PK parameters for statins.
CLASS: STATINS
Reference
Model N
Obs.
Drug
Nawral et
al.(155)
Atorvastatin
2
26
Drug
Simonson et
al.(156)
Rosuvastatin
1
6
Simonson et
al.(156)
1
6
Simonson et
al.(156)
1
6
Population
characteristics
θCL
(L/h)
CV
%
θV (L)
CV
%
Patients who had
experienced
muscular adverse
effects due to
statin therapy
504
34.4
3250
67.1
Patients with
9.18
normal hepatic
function
Patients with mild 7.38
hepatic
impairment
Patients with
6.36
moderate hepatic
impairment
35.0
Table 26. Significant covariates for CL and V of statins
CLASS: STATINS
Covariates
AST
Drugs
Atorvastatin(155)
44.0
66.0
θka
(h-1)
CV
%
θQ(L
/h)
1880
CV
%
θVp (L)
CV%
2170
19.7
Table 27. Summary of population PK parameters for antihypertensives.
CLASS: ANTIHYPERTENSIVES
Reference
Model N
Obs.
Drug
Flynn et
al.(157)
Amlodipine
1
73
θV (L) CV
%
θka
(h-1)
CV
%
Hypertensive
children and
adolescents
23.7a
14.9
1150
49.4
0.790
50.7
Hypertensive
children and
adolescents
26.5a
19.28b
43.2
1130
48.7
0.807
50.6
83.4
39.0
9.3
1.29
51.1
259c
49.4
0.594
179.0
2.30
38.6
1050c
44.4
1.08
149.0
63.8
27.4
210
1
Drug
Pfister et
al.(158)
Candesartan cilexetil
2
8
Hypertensive
patients on
regular
haemodialysis
Carvedilol
1
58
151
Japanese patients
with chronic
heart failure (Renantiomer)
1
58
155
Japanese patients
with chronic
heart failure (Senantiomer)
Furosemide
1
23
198
Patients with
congestive heart
failure
Saito et
al.(159)
Drug
Carlton et
al.(160)
405
θCL (L/h) CV
%
Flynn et
al.(157)
Drug
Saito et
al.(159)
73
405
Population
characteristics
θQ(L
/h)
CV
%
θVp (L)
17.6b
1.75
0.029
9.9
117.3
CV%
Drug
Thomson et
al.(161)
Lisinopril
1
140
880
Elderly and renal 0.251
disease patients
with
hypertension
52.0
Drug
Yoshihara et
al.(162)
Olmesartan
2
472
7911
Healthy
volunteers and
hypertensive
patients
7.320
6.0
Drug
Tatami et
al.(163)
Telmisartan
2
149
1566
59.3
189.0 202.8
119.0 0.38
80
88.3
Tatami et
al.(164)
2
7487
Healthy
volunteers and
hypertensive
patients
Japanese and
western
hypertensive
patients
39.8
67.7
132.3 0.303
84.6
101.0 1257
Drug
Habtemariam
et al.(165)
Valsartan
2
26
2.87
131.0 8.36
65.5
51.8
Habtemariam
et al.(165)
2
26
4.74
39.0
16.3
39.7
9.13
Habtemariam
et al.(165)
2
26
Hypertensive
paediatric
patients
Hypertensive
paediatric
patients
(using weight)
Hypertensive
paediatric
patients
(using fat free
4.32
32.7
15.3
30.9
7.6
1343
36.7
127.0 0.104
1.46
181.3
73.0
6.0
1060
86.8
218.9
mass)
a: male; b:female; c: L/h/kg
Table 28. Significant covariates for CL of antihypertensives.
CLASS: ANTIHYPERTENSIVES
Covariates
Drugs
Amlodipine(157)
Creatinine clearance
Valsartan(165)
Fat free mass
Amlodipine(157), valsartan(165)
Weight
Table 29. Summary of population PK parameters for antibiotics.
CLASS: ANTIBIOTICS
Reference
Model N
θV (L)
CV
%
θka
(h-1)
CV
%
Adult and
2.4
paediatric patients
from intensive
care unit
Adult patients
5.0
with
haematological
malignancies
39.7
10.7
8.1
0.1
27.4
59.7
30.1
17.0
Neonates with
immature renal
function
35.5
0.9
42.5
Population
characteristics
Drug
Bressolle et
al.(166)
Amikacin
2
56
801
Romano et
al.(167)
1
149
Drug
Kimura et
al.(168)
Arbekacin
1
83
207
CV
%
Obs.
310
θCL
(L/h)
0.1
θQ(L
/h)
CV
%
θVp (L)
CV%
Tanigawara
et al.(169)
2
375
Drug
Forrest et
al.(170)
Ciprofloxacin
2
74
Payen et
al.(171)
2
37
216
Schaefer et
al.(172)
Drug
Rosario et
al.(173)
Izquierda et
al.(174)
Drug
Jauregizar et
al.(175)
2
10
232
Netilmicin
2
62
310
Fattinger et
al.(176)
Drug
Xuan et
al.(177)
Aarons et
al.(178)
2
258
Gentamicin
2
210
1
378
97
74
Tobramycin
1
327
575
2
322
97
38.8
0.2b
38a
24.0
0.7b
2.01
96.5
1.8b
76.9
0.4
102.5 0.4
1.0b
8.8
7.8
0.7b
22.6
0.6
31.9
1.3b
Adults patients
0.9
with cancer
Paediatric patients 0.07
with infection
18.5
8.6
28.2
60.4
0.9
51.3
Adult patients
3.9
undergoing
urological surgery
Neonate patients
0.2
42.0
14.5
56.0
19.0
0.5b
12.0
Adult hospitalized 4.5
patients
Adult patients
0.059
who need
37.0
27.3
28.5
32.0
0.327
3.0
1581 Healthy subjects,
patients with
MRSA and
renally impaired
patients
Adults with
critically ill
patients
Paediatric and
adolescents
patients with
acute infections
Children with
cystic fibrosis
37.1
164.6
17a
10.1
0.51b
10.2
0.4b
14.9
tobramycin
monitoring
Vancomycin
Drug
Llopis-Salvia 2
50
&JinemezTorres(179)
Dehoog et
al.(180)
1
108
337
Adult patients
0.034
with infection
with VANsensitive
microorganism
Paediatric patients 0.06c
<1 month with
suspected central
line-related
29.2
0.4b
36.4
31.0
0.4b
25.0
0.02
1.3
a: units of L/h/1.73m2; b: units of L/kg; c: units of L/h/kg
Table 30. Significant covariates for CL of antibiotics.
CLASS: ANTIBIOTICS
Covariates
Age
Body surface area
Creatinine clearance
Gestational age
Height
Renal clearance
Sex
Total protein
concentration
Weight
References
Amikacin(166),(167), arbekacin(169), ciprofloxacin(171), gentamicin(173), tobramycin(177)
Ciprofloxacin(170)
Amikacin(166),(167), netilmicin(175), tobramycin(177)
Arbekacin(169), gentamicin(173), netilmicin(176), vancomycin(180)
Amikacin(166), gentamicin(173), tobramycin(177)
Ciprofloxacin(170)
Amikacin(166), arbekacin(169), ciprofloxacin(171), gentamicin(173), netilmicin(175), tobramycin(177)
Amikacin(166)
Amikacin(166), arbekacin(169), ciprofloxacin(171), gentamicin(173), netilmicin(176), tobramycin(177)
39.8
Table 31. Significant covariates for V of antibiotics.
CLASS: ANTIBIOTICS
Covariates
Age
Body surface area
Gestational age
Height
Sex
Total protein
concentration
Weight
References
Amikacin(166),(167), arbekacin(169), ciprofloxacin(171), gentamicin(173), tobramycin(177)
Ciprofloxacin(170)
Arbekacin(169), gentamicin(173), netilmicin(176), vancomycin(180)
Amikacin(166), gentamicin(173), tobramycin(177)
Amikacin(166), arbekacin(169), ciprofloxacin(171), gentamicin(173), netilmicin(175), tobramycin(177)
Amikacin(166)
Amikacin(166), arbekacin(169), ciprofloxacin(171), gentamicin(173), netilmicin(176), tobramycin(177)
Table 32. Summary of population PK parameters of drugs estimated with 3 compartmental models.
Reference
N
Drug
Kuiper et
al.(133)
Lignocaine
31 442 Adult patients
undergone
opthalmic
surgery with
general
anaesthesia
Drug
Zomorodi
et al.(52)
Midazolam
63 1681 Adult patients
sedated after
CABG
Propofol
270 4112 Adult surgical
patients
Drug
Schuttler
&
Ihmsen(1
36)
Yamashita 36
et al.(134)
Li et
al.(135)
76
Obs.
323
Population
characteristics
Adult patients
with major
burn
1439 Adult surgical
patients
θCL1
(L/h)
CV
%
θV1 (L) CV
%
θCL2
(L/h)
CV
%
θV2(L)
CV
%
θCL3
(L/h)
CV
%
θV3
(L)
CV
%
0.011
18.0
1.29
44.0
0.015
19.0
7.39
32.0
0.125
25.0
57.3
24.0
40.0
33.0
60.0
37.3
49.0
24.0
15.8
55.0
365
85.0
0.024
37.4
9.3
40.0
0.375
51.9
44.2
54.8
0.0153
50.9
26.6
46.9
0.07
16.8
48.4
0.0487
55.4
70.8
0.0593
42.3
220
56.4
0.026
24.5
12.1
0.006
45.5
213
0.0123
30.8
43
27.7
27.4
62.8
Table 33. Summary of mean CV% values of population pharmacokinetic parameters.
One compartment
Drug classes
Two compartments
CL CV% (n)
V CV% (n)
CL CV% (n)
Vc CV% (n)
Cardiovascular drugs
Anticoagulants
34.5 (19)
39.7 (8)
57.2 (5)
36.8 (3)
Antiarrhythmics
30.1 (3)
38.2 (4)
32.0 (9)
41.3 (5)
Antiplatelets
34.9 (3)
39.2 (3)
-
-
Statins
48.3 (3)
-
34.4 (1)
67.1 (1)
Antihypertensives
37.9 (6)
63.8 (5)
63.9 (8)
68.4 (6)
Psychotropics
Anticonvulsants
25.5 (25)
32.3 (18)
-
-
Antipsychotics
53.2 (12)
69.5 (11)
98.9 (2)
30.0 (1)
Antidepressants
47.5 (7)
123.4 (6)
-
-
Other psychotropics
28.0 (3)
61.0 (2)
51.7 (5)
103.0 (4)
Immunosuppressants
37.6 (28)
45.2 (28)
39.4 (37)
51.9 (33)
Antibiotics
44.7 (5)
32.9 (5)
34.8 (10)
31.1 (9)
n= number of studies
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