Antibiotics in severely malnourished children: systematic review of efficacy, safety and pharmacokinetics
Marzia Lazzerini & David Tickell
Volume 89, Number 8, August 2011, 594-607
Table 4. Pharmacokinetics of second-line parenteral antibiotics in children with severe acute malnutrition
| Reference | Drug, dose (per kg), route | No. of children | Cmax (μg/ml) and Tmax (min) |
Vd (l/kg) |
Clearance (ml/kg/h) |
Half life (min) |
AUC (μg.min/ml) |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Malnourished | Eutrophic | Malnourished | Eutrophic | Malnourished | Eutrophic | Malnourished | Eutrophic | Malnourished | Eutrophic | ||||||||
| Bolme et al. 1995 |
Benzylpenicillin, 30 mg, IV | 29 | – | – | U: 1.47 K: 1.18 M: 0.91 MK: 0.93 |
1.39 | CL U: 15.1* CL K: 16.9* CL M: 14.0* CL MK: 11.6* |
CL 22.2 | U: 67.8 K: 44.8 M: 44.8 MK: 55.7 |
43.4 | U: 1993.3 K: 1 769.2 M: 2 138.2 MK: 2 594.4 |
1351.3 | |||||
| Procaine penicillin G, 30 mg, IM | 18 | Tmax same in all groups (30–60 min) | – | – | – | – | M: 139.1 MK: 264.9 |
177.4 | Same in all groups (no values given) | ||||||||
| Bolme et al. 1980 |
Benzylpenicillin, 50 000 IU, IV | 16 | K Cmax at 2 h: 3.1 M Cmax at 2 h: 4.1 MK Cmax at 2 h: 10.2 |
N Cmax at 2 h: 1.4** | – | – | Trend to slower CL in malnourished | – | – | – | – | – | |||||
| Benzylpenicillin, 16 000 IU, IM | 13 | Tmax < 30 m all groups Cmax > 10 μg all groups |
– | – | Trend to slower CL in malnourished | – | – | – | – | – | |||||||
| Buchanan et al. 1979 |
Penicillin G, 25 000 IU, IV | 8 | – | – | Day 0: 1.6 Day 21: 1.4 |
D0: 183* D21: 286* |
– | D0: 57* D21: 32* |
– | – | – | ||||||
| Seaton et al. 2007 |
Gentamicin, 7.5 mg, IM | 34 | 100% > 8.0 μg/ml at 2 hour 76% > 12.0 μg/ml at 2 hour |
– | 0.67 | – | CL 1.67a Trough level: 98% < 1.0 mg/l at 20 ha |
– | 84 | – | – | – | |||||
| Samotra et al. 1985 |
Gentamicin, 4.0 mg, IM | 10 | Cmax 8.9 at 30 min | Cmax 10.02 at 30 min | – | – | – | – | 373 | 199 | 22.40 | 22.32 | |||||
| Khan et al. 2006 |
Gentamicin, 5.0 mg, IM | 310 | od: Cmax 11.7 at 60 min* tds: Cmax 4.7 at 60 min* |
– | – | – | Trough level at 24 h: od: 0.29 mg/l* tds: 0.48 mg/l |
– | – | – | – | – | |||||
| Bravo et al. 1982 |
Gentamicin, 3.5 mg, IV | 18 | Cmax 6.31 at 29.67 min* | Cmax 8.39 at 24 min | 0.46* | 0.39 | CL 3.99 | CL 3.57 | 82 | 75 | No difference (no values given) | ||||||
| Buchanan et al. 1979 |
Gentamicin, 2.4 mg, IV | 6 | – | – | D0: 3.9 D21: 4.36* |
– | D0: CL 13.6 ml/kg D21: CL 28.7 ml/kg* |
– | D0: 229 D21: 179* |
– | – | – | |||||
AUC, area under the plasma concentration time curve; CL, clearance; Cmax, maximum concentration; D0, day 0 (admission); D21, day 21 (recovery); IM, intramuscular; IU, international units; IV, intravenous; K, kwashiorkor; M, marasmus; MK, marasmic kwashiorkor; N, normal (controls); od, once daily dosing; tds, three times daily dosing; Tmax, time to maximum concentration; U, underweight; Vd, volume of distribution.* P < 0.05; **P-value not specified.
a One child who was in shock had a trough level of 5.5 μg/ml; longer clearance was noted in children with hypothermia, high serum creatinine or large base excess.