Journal Article

Extended-Interval Gentamicin Administration in Malnourished Children

A. M. Khan, T. Ahmed, N. H. Alam, A. K. Chowdhury and G. J. Fuchs

in Journal of Tropical Pediatrics

Volume 52, issue 3, pages 179-184
Published in print June 2006 | ISSN: 0142-6338
Published online August 2005 | e-ISSN: 1465-3664 | DOI: http://dx.doi.org/10.1093/tropej/fmi085
Extended-Interval Gentamicin Administration in Malnourished Children

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Malnourished children have several physiologic abnormalities that can affect drug distribution and elimination. The aim of this study was to determine the efficacy, safety and pharmacokinetics of a once-daily dose of gentamicin compared with conventional thrice-daily dosing in malnourished children. To our knowledge, it has not been investigated in this population so far. A total of 310 malnourished children of either gender aged 6 months to 5 years with diarrhea and pneumonia were randomized to receive intramuscular gentamicin 5 mg/kg/day once-daily (OD) (n=148) or the same total daily amount given in three divided doses (TD) (n=162) in addition to ceftriaxone 75 mg/kg/day. After 48 h at steady state, gentamicin pharmacokinetics was assessed by fluorescence polarization immunoassay in a subgroup of 59 children and 43 children in the OD and TD groups, respectively. The groups were equivalent in baseline demographic, clinical and laboratory characteristics. Good and partial clinical responses occurred in 64 per cent vs. 54 per cent and 25 per cent vs. 27 per cent in the OD and the TD children, respectively (p=NS for both comparisons). Five patients in each treatment group died. Renal toxicity defined by change in serum creatinine was not observed in any patient from either group. In the OD group, mean±sd serum gentamicin concentrations at 1 (peak), 3, 5, 8, 23, and 24 (trough value) hours after the dose were 11.7±4.1, 4.4±1.2, 2.08±0.9, 1.01±0.6, 0.31±0.09 and 0.29±0.07 mg/l respectively. In the TD group, mean ±sd serum gentamicin concentration at 1 hour (peak) was 4.7±1.8 mg/l and the trough concentration was 0.48±0.21 mg/l. In OD group, the gentamicin trough concentration was significantly lower (p<0.001) and the peak concentration was significantly higher (p<0.001) compared to TD group. The results of this study indicate that once-daily gentamicin is effective and safe in malnourished children. Widespread implementation of once-daily dosing in malnourished children is appropriate and will reduce number of intramuscular injections and hospital costs.

Journal Article.  3342 words. 

Subjects: Paediatrics

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