Table 6.
Pharmacokinetic parameters of aminoglycosides. Figures are the mean or range.
| Gestational age (weeks) | Daily dose (mg/kg) | Cl (mL/min/kg) | Vd (L/kg) | t1/2 (h) | Peak conc. (µg/mL) | Trough conc. (µg/mL) | Ref. |
|---|---|---|---|---|---|---|---|
| Gentamicin | |||||||
| 26–32 | 2.5 every 18 h | 0.93 mL/min | na | 12.0 | 6.3 | 1.6 | [70] |
| 26 | 2.5 | 0.53 | 0.50 | 10.2 | 5.9 | 1.3 | [81] |
| 31 | 3.0 | 0.62 | 0.49 | 8.9 | 6.8 | 1.2 | |
| 38 | 4.0 | 0.78 | 0.46 | 7.0 | 8.9 | 1.3 | |
| 34 | 2.5 × 2 | na | na | na | 3.8 | 2.8 | [82] |
| 34 | 4 | na | na | na | 5.9 | 1.6 | |
| p | --- | --- | --- | --- | <0.001 | <0.05 | |
| 36 | 2.5 × 2 | na | na | na | 6.4 | 2.2 | [83] |
| 35 | 5 | na | na | na | 9.5 | 1.4 | |
| p | --- | --- | --- | --- | <0.001 | <0.005 | |
| 37–41 | 2.5 × 2 | na | na | 5.9 | 6.4 | 1.9 | [84] |
| 37–41 | 4 | na | na | 5.5 | 8.2 | 0.9 | |
| p | --- | --- | --- | na | <0.001 | <0.0001 | |
| 29 | 2.5 | na | 0.76 | 11.1 | 6.0 | 1.25 | [73] |
| 28 | 5 every 48 h | na | 0.76 | 10.7 | 8.1 | 1.72 | |
| p | --- | --- | NS | NS | <0.0001 | <0.001 | |
| 27 | 2.5 | na | 0.61 | 10.0 | 5.8 | 1.2 | [74] |
| 27 | 5 every 48 h | na | 0.66 | 10.3 | 8.0 | 0.7 | |
| p | --- | --- | NS | NS | <0.01 | NS | |
| Netilmicin | |||||||
| <34 | 4.5 | 1.5 (mL/min) | 0.46 | 7.6 | 6.7 | 1.2 | [85] |
| 34–36 | 4.5 | 1.33 (mL/min) | 0.51 | 8.5 | 8.6 | 1.4 | |
| >36 | 4.5 | 3.16 (mL/min) | 0.51 | 6.1 | 7.2 | 0.9 | |
| 29 | 6 | 0.45 | 0.52 | 6.6 | 5.0 | 2.7 | [86] |
| 35 | 6 | 0.45 | 0.46 | 6.7 | 6.2 | 2.8 | |
| 40 | 6 | 0.64 | 0.41 | 4.6 | 6.6 | 1.9 | |
| 35 | 3 (IM) | na | 0.61 | 4.7 | 5.6 | 2.7 | [87] |
| 28 | 6 every 36 h | na | na | 17.8 | 10 | 4.8 | [88] |
| 30 | 2.5 × 2 | 0.84 | 0.60 | 8.6 | 9.0 | 2.8 | [89] |
| 35 | 2.5 × 2 (IM) | 1.06 | 0.34 | 9.6 | 7.7 | 2.6 | [90] |
| Tobramycin | |||||||
| 28 | Note A | 0.69 | 0.59 | 9.9 | 7.6 | 1.7 | [92] |
| 29 | Note B | 0.72 | 0.74–0.94 | 8.3–12.8 | 4.6–8.4 | 1.2–2.0 | [93] |
| na | 5 (IM) | 4.9 (mL/min) | 0.49 | 4.4 | 2.7 | na | [94] |
| Amikacin | |||||||
| 36 | 7.5 (IM) | 1.42 | 0.66 | 6.0 | 18.6 | na | [97] |
| 32 | 5 (IM) | 0.96 | 0.72 | 9.0* | na | na | [98] |
| 40 | 1.24 | 0.56 | 0.55 | 5.5* | na | na | |
| 34 | 5 (IM) | 0.86 | 0.49 | 6.8 | na | na | [99] |
| 30 | Note A | 0.84 | 0.57 | 8.4 | 23.9 | 8.3 | [100] |
| 37 a | Note B | 2.05 | 0.34 | 2.8 | 6.8–35.7 | <0.8–17.7 | [101] |
| 38 | 7.5–10 | 1.71 | 0.64 | 3.7 | na | na | [102] |
| 27b | Note E | 0.36 d | 0.63 d | 16.4 d | 47.7 d | 9.9 d | [105] |
| 28 c | Note E | 0.60 d | 0.59 d | 12.4 d | 40.9 d | 6.2 d | |
| p | NS | <0.005 | NS | <0.02 | NS | <0.01 | |
na = not available. NS = not significant. IM = intramuscular. a The postnatal age was 450 days and the body weight was 7.4 kg. b Ibuprofen. c Placebo. d Median. * p = 0.009. Note A: 2.5 mg/kg every 18 h or 3 mg/kg every 24 h. Note B: 2.5 mg/kg every 12 or 18 h. Note C: 7.5 mg/kg every 12 h when the chronologic life was up to 7 days and 7.5 mg/kg every 8 h when the chronologic life was >7 days. Note D: the loading dose was 11.7 ± 1.3 and the maintenance dose was 9.8 ± 1.4 mg/kg. In the first drug dosing regimen, neonates received a loading dose of 10 mg/kg amikacin followed by a maintenance dose of 7.5 mg/kg every 12 h. The infants and children received 7.5 mg/kg amikacin every 12 h. In the second drug dosing regimen, we considered an infusion of 15 mg/kg amikacin every 12 h for neonates, infants and children. Note E: 20 mg/kg every 36 h when gestational age was <30 weeks and 20 mg/kg every 24 h when gestational age was ≥30 weeks.