Table 2.
Pharmacokinetic information on fentanyl in children [8, 24, 29, 32, 33, 37, 39–41, 43, 55, 56, 67, 75, 79, 88, 90, 92, 93, 103, 136, 181–187].
| n | Age | Weight (kg) | Dose (μg/kg) | Route | CL (mL/min/kg) | t1/2 (min) | V (L/kg) | Comp | No of samples | Lab method | Remarks | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 2 | 1 ± 0 days | 3.2 ± 1.1 | 30.3 ± 16.0 | IV, 2–10 min | 16.2 ± 2.59* | 294 ± 113 | 5.94 ± 1.47** | 2 | 13/ 10h | RIA | Age 0–1 month | [24] |
| 2 | 7 ± 0.056 months | 6.0 ± 1.2 | 19.1 ± 14.5 | IV, 2–10 min | 18.1 ± 1.41* | 233 ± 137 | 4.45 ± 1.64** | 2 | 13/ 10h | RIA | Age 1 month-1 year | [24] |
| 6 | 3.17 ± 0.68 years | 17.3 ± 3.4 | 10.0 ± 3.1 | IV, 2–10 min | 11.5 ± 4.19* | 244 ± 79 | 3.06 ± 1.02** | 2 | 13/ 10h | RIA | Age 1–5 years | [24] |
| 3 | 12 ± 1.73 years | 58.3 ± 13.3 | 4.3 ± 1.2 | IV, 2–10 min | 7.05 ± 1.24* | 208 ± 71 | 1.92 ± 1.04** | 2 | 13/ 10h | RIA | Age 10–14 years | [24] |
|
| ||||||||||||
| 19 | 3.2 ± 4.2 years | max 3.6 ± 3.1/h | IV, 5 min; cont. 70.5 (7–144) h | 13.2 ± 9.6 | 1266 | 15.2 | non | > 11 | RIA | all patients, cont. sedation | [33] | |
| 5 | 0.14 ± 0.08 years | max 4.3 ± 3.7/h | IV, 5 min; cont. 72.6 (48–144) h | 8.2 ± 4.6 | non | > 11 | RIA | Age < 6 monthsa) | [33] | |||
| 9 | 1.4 ± 1.1 years | max 3.9 ± 3.3/h | IV, 5 min; cont. 70.9 (19–136) h | 18.9 ± 11.0 | non | > 11 | RIA | Age 6 months to 6 years | [33] | |||
| 5 | 9.5 ± 2.8 years | max 2.5 ± 2.3/h | IV, 5 min; cont. 68.2 (7–136) h | 8.0 ± 3.9 | non | > 11 | RIA | Age > 6 yearsa) | [33] | |||
|
| ||||||||||||
| 15 | 1d – 10.9 yearsc) | 2/ 9 ± 7/h | IV, bolus, cont. 91b) (37–211) h | 19.3 ± 12.4 | 954 ± 606 | 17.2 ± 14.7 | non | > 8/ > 48h |
RIA | comparison of fentanyl and alfentanil | [136] | |
|
| ||||||||||||
| 14 | 3 ± 1 daysd) | 2.9 ± 0.2d) | 10–50 | IV, 1–3 min | 17.94 ± 4.38d) | 317 ± 70d) | 5.1 ± 1.0d) | 2 | > 8/ 18h |
RIA | all patients | [29] |
| 4 | 0.6 ± 0.13 daysd) | 3.5 ± 0.2d) | 10–50 | IV, 1–3 min | 28.00 ± 11.00d) | 188 ± 85d) | 4.66 ± 1.74d) | 2 | > 8/ 18h |
RIA | Myelomeningocele repair | [29] |
| 4 | 7.0 ± 2.48 daysd) | 2.5 ± 0.5d) | 50 | IV, 1–3 min | 21.43 ± 9.15d) | 213 ± 37d) | 5.87 ± 2.65d) | 2 | > 8/ 18h |
RIA | Thoracic surgery | [29] |
| 6 | 1.8 ± 0.5 daysd) | 2.7 ± 0.3d) | 25–50 | IV, 1–3 min | 9.00 ± 1.00d) | 473 ± 132d) | 4.88 ± 1.42d) | 2 | > 8/ 18h |
RIA | Abdominal surgery | [29] |
|
| ||||||||||||
| 9 | 1.1 ± 0.3 | 30 | IV, 1 min | 1062 ± 558 | 3/ 6–9h |
GLC [181] |
Preterm and term infants, GA 23–38 wks | [41] | ||||
|
| ||||||||||||
| 14 | 18.3 ± 23.6 days | 2.7 ± 0.5 | 54.1 ± 2.3 | IV, 2 min | 22.4 ± 8.2 | 325.8 ± 181.8 | 8.3 ± 2.4 | 2/3 | 23/ 12h |
RIA [182, 183] |
all patients | [32] |
| 3 | 13.3 ± 20.3 days | 2.9 ± 0.4 | IV, 2 min | 21.1 ± 8.5 | 336.3 ± 193.4 | 8.1 ± 2.5 | 2/3 | 23/ 12h |
RIA [182, 183] |
Preterm infants, GA < 36 wks | [32] | |
| 11 | 36.7 ± 30.4 days | 2.0 ± 0.1 | IV, 2 min | 26.2 ± 7.1 | 294.3 ± 173.9 | 9.0 ± 2.7 | 2/3 | 23/ 12h |
RIA [182, 183] |
Neonates | [32] | |
|
| ||||||||||||
| 20 | 1.7 ± 0.8 | 5–12.5/ 0.68 ± 0.24/h |
IV, 10 min, cont. 86 ± 47 h | RIA | all patients, GA 32.5 ± 3.6 wks | [43] | ||||||
| 12 | 5–12.5/ 0.64 ± 0.19/h |
IV, 10 min, cont. 93 ± 55 h | 12.1 ± 15.4 | RIA | Preterm infants, GA < 34 wks | [43] | ||||||
| 8 | 5–12.5/ 0.75 ± 0.30/h |
IV, 10 min, cont. 75 ± 24 h | 13.0 ± 19.8 | RIA | Preterm and term infants, GA ≥ 34 wks | [43] | ||||||
|
| ||||||||||||
| 7 | 16 ± 9 days | 1.9 ± 1.1 | 1.28 ± 0.58/h | IV, cont. 111 (48–206) h | 19.2 ± 8.2 | 570 ± 156 | 17 ± 9 | 1 | 5 | GC-MS [184] |
Preterm and term infants GA 27–39 wks; Cmax 0.7–2 ng/mL | [39] |
|
| ||||||||||||
| 38 | 10 (5; 21) hourse) | 1.8 (1.2; 2.6)e) | 10.5/h/ 1.5/h |
IV, cont. 58 (45; 78) he) | 11.5 ±
4.0 (4.6–18.5) |
non | 5/ 60h |
RIA [185] |
Preterm and term infants, GA 26–42 wks | [40] | ||
|
| ||||||||||||
| 1 | 15 months | ~ 8 | 50/ 18/h |
IV, bolus, cont. 123 min | 7.3 | 173 | 1.85 | 14/ ~5h |
GLC [56, 181] |
Case report, renal failure, CPB | [55] | |
| 1 | 3 years | 10.2 | 1.64/ 18/h |
IV, bolus, cont. 136 min | 0.41 | 4620 | 0.142 | 8 ~5h |
GLC [56, 181] |
Case report, Wilm’s tumor | [55] | |
|
| ||||||||||||
| 10 | 18.9 ± 15.8 months | 8.6 | 50/ 9–18/h |
IV, 1 min; cont. 112 (81–141) min | 12.8 ± 7.3 | 141 ± 98 | 1.385 ± 0.875 | 2 | GLC [181] |
CPB | [56] | |
|
| ||||||||||||
| 19 | 3.54 years (5 months – 16 years) |
13.2 (3.5 – 50) |
30–50/ 9–18/h |
IV, bolus; cont. | 13.3 ± 6.5 | 102 ± 85 | 1.203 ± 0.777 | 2 | > 9/ > 2h |
GLC [181] |
CPB | [67] |
|
| ||||||||||||
| 12 | 5.5 ± 11.5 days | 3.2 ± 0.6 | 5–10/ 3.3 ± 1.6/h |
IV, bolus; cont. | non | 11 | RIA | all patients, CPB, ECMO | [75] | |||
| 9 | 6.7 ± 13.3 days | 3.2 ± 0.6 | 5–10/ 3.2 ± 1.7/h |
IV, bolus; cont. | 25.3 ± 41.9 | non | RIA | Survivors, CPB, ECMO | [75] | |||
| 3 | 2 ± 1.7 days | 3.1 ± 0.8 | 5–10/ 3.6 ± 1.3/h |
IV, bolus; cont. | 8.1 ± 12.8** | non | RIA | Non-survivors, CPB, ECMO | [75] | |||
|
| ||||||||||||
| 130 | 5.9e) months (1.2–28.4) | 6.4e) (3.7–11.6) | 2.67e) (1.46–4.08)/h | IV, bolus/ cont. | 14.8e) (5.7–24.0) | 2 | 6e) (4–10) | MS | all patients, Pop-PK, covariate model | [37] | ||
| 121 | 5.1e) months (1.0–21.8) | 6.1e) (3.7–9.9) | 2.79e) (1.67–4.17)/h | IV, bolus/ cont. | 5.9 | 2 | 6e) (4–11) | MS | < 40kg, Pop-PK, allometric theory-based model | [37] | ||
| 93 | 8.1e) months (3.7–35.0) | 7.6e) (5.1–12.8) | 2.63e) (1.63–3.75)/h | IV, bolus | 7.4 | 2 | 5e) (4–8) | MS | bolus only, Pop-PK, allometric theory-based model | [37] | ||
|
| ||||||||||||
| 6 | 16.6 ± 1.5 years | 137.4 ± 14.3 | 1.00 ± 0.36 | IV, bolus | 11.2 ± 2.6 | 290 ± 118 | 4.7 ± 2.1 | non | ≥ 10/ 24 h |
LC-MS/MS [8] |
Obese adolescents | [79] |
|
| ||||||||||||
| 13 | 14b) (3–36) months | 11b) (5–17) | 2/ 1.12/h/ 0.375/h |
EPI, cont. 38.0b) (37.3–38.8) h | 334b) (137–1730) | non | 6 | LC-MS/MS [186, 187] |
t1/2 calculated based on MRT: 954b) (215–1892) min | [88] | ||
| 11 | 68b) (45–131) months | 21b) (16–52) | 2/ 1.12/h/ 0.375/h |
EPI, cont. 38.0b) (35.5–39.0) h | 358b) (206–563) | non | 6 | LC-MS/MS [186, 187] |
t1/2 calculated based on MRT: 478b) (425–796) min | [88] | ||
|
| ||||||||||||
| 21 | 5.5 ± 1.3 years | 20.9 ± 5.7 | 12.2 ± 1.09 | OTFC | 17.5 | 2.44 | 2 | > 3 ≤ 4 h |
RIA [182] |
OTFC bioavailability 33% | [90] | |
| 21 | 5.5 ± 1.3 years | 20.9 ± 5.7 | 12.2 ± 1.09 | OTFC | 46.0 ± 16.0f) | 168 ± 90 | 9.8 ± 4.1f) | non | > 3 ≤ 4 h |
RIA [182] |
Cmax 1.60 ± 0.55 ng/mL,
tmax 59 ± 32 min; AUC 5.03 ± 2.20
h*ng/mL |
[90, 93] |
|
| ||||||||||||
| 17 | 6.7 ± 4.9 years | 21.5 ± 4.9 | 12.7 ± 1.2 | OTFC | 15.2 ± 6.3 | 276 | 4.9 ± 2.8 | 2 | 12 ± 1/ 3.67 h |
RIA [182] |
OTFC bioavailability 36%, Cmax 1.03
± 0.31 ng/mL, tmax 53 ± 40 min; CL, t1/2 and VdSS data combined with [90], n=38 |
[90, 92] |
| 17 | 6.7 ± 4.9 years | 21.5 ± 4.9 | 12.7 ± 1.2 | OTFC | 68.5 ± 39.8f) | 198 ± 222 | 11.6 ± 6.6f) | non | RIA [182] |
Cmax 1.06 ± 0.31 ng/mL, tmax 56 ± 41 min, AUC 4.54 ± 3.60 h*ng/mL | [92, 93] | |
|
| ||||||||||||
| 38 | 6.3 ± 1.6 years | 12.4 ± 1.04 | OTFC | 57.7 ± 32.3f) | 184 ± 168 | 10.7 ± 5.5f) | non | RIA [182] |
Combined data, Cmax 1.32 ± 0.51 ng/mL, tmax 58 ± 36 min, AUC 4.78 ± 2.96 h*ng/mL | [90, 92, 93] | ||
|
| ||||||||||||
| 10 | 7.9 ± 1.94 years | 28.2 ± 10.2 | 13.9 ± 1.41 | PO | 55.5 ± 37.5f) | 282 ± 168 | 17.5 ± 7.20f) | non | 16 (8–16)/ 10 h |
LC-MS/MS | Cmax 1.83 ± 1.19 ng/mL, tmax 104 ± 98 min, AUC 6.46 ± 3.96 h*ng/mL | [93] |
|
| ||||||||||||
| 8 | 42.4 ± 16.4 months | 14.6 ± 2.9 | 1.72/h (Patch 25 μg/h) |
TD | 867 ± 373 | 18/ 144 h |
RIA [182] |
Cmax 1.64 ng/mL, tmax 1080 min, AUC 91.75 h*ng/mL, Css 1.32 ng/mL | [103] | |||
a)
mean clearance values of the youngest and the oldest children were switched in the results section of the publication and recalculated for this review
b)
median data (range)
c)
demographics also include alfentanil group
d)
mean ± SEM
e)
median data (interquartile range)
f)
CL/V and V/F
Reported statistical significance is indicated as follows:
*
p < 0.05,
**
p < 0.005,
***
p < 0.001.
Abbreviations: EPI epidural, IV intravenous, OTFC oral transmucosal fentanyl citrate, PO per os, TD transdermal