Bulletin of the World Health Organization

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 3. Pharmacokinetics of first-line oral antibiotics in children with severe acute malnutrition

Reference Drug, dose (per kg) No. of children Absorption (%)
Cmax (μg/ml) and Tmax (min)
Vd (l/kg) protein binding (%)
Clearance (ml/kg/h)
Half life (min)
AUC (μg.min/ml)
Malnourished Eutrophic Malnourished Eutrophic Malnourished Eutrophic Malnourished Eutrophic Malnourished Eutrophic Malnourished Eutrophic
Bolme et al. 199530 Penicillin V, 20 mg 47 U (f): 35.9*
U (nf): 29.8*
M (f): 66.1*
M (nf): 22.7*
K (f): 82.6*
K (nf): 27.1*
f: 54.8
nf: 47.0
U Ka (f): 9.5*
U Ka (nf): 3.9*
M Ka (f): 8.4*
M Ka (nf): 0.8*
K Ka (f): 2.5*
K Ka (nf): 1.6*
Ka (f): 10.1
Ka (nf): 2.2
U (f): 40.8*
U (nf): 62.7*
M (f): 54.2*
M (nf): 145.2*
K (f): 139.6*
K (nf): 109.6*
f: 39.1
nf: 75.6
U (f): 476.7*
U (nf): 396.0*
M (f): 941.7*
M (nf): 323.2*
K (f): 975.2*
K (nf): 319.5*
f: 493.6
nf: 423.4
Zerihun et al. 199131 Amoxicillin, 25 mg 15 M Tmax: 60
K Tmax: 120**
Tmax: 60
(all groups adequate Cmax, no values given)
Bolme et al. 198032 Penicillin V, 30 000 IU 16 SAM Tmax: 120
SAM Cmax: 5.8
Tmax: 90
Cmax: 4.3
Buchanan 197733 Benzyl-penicillin, dose NS Adult serum versus pooled serum of 24 kwashiorkor children % free drug similar (N: 59.1%, K: 64.0%) so Vd likely unaffected
TMP-SMX PB: N: 71.9%, K: 93–96%
Bravo et al. 198434 SMX, 22 mg 17 Cmax: 41.4
Tmax: 120
Cmax 36.8
Tmax 150
Vd: 0.529 Vd: 0.529 41 83 9.4 * 4.9 9.55 * 5.47

AUC, area under the plasma concentration time curve; Cmax, maximum concentration; f, fasting; IU, international units; K, kwashiorkor; Ka, absorption rate constant; M, marasmus; MK, marasmic kwashiorkor; n, normal (controls); nf, non-fasting; NS, not stated; PB, protein binding; SAM, severe acute malnutrition; SMX, sulfamethoxazole; Tmax, time to maximum concentration; TMP, trimethoprim; U, underweight; Vd, volume of distribution; * P < 0.05; ** P-value not specified.