Comparing pharmacokinetics of amoxicillin given twice or three times per day to children older than 3 months with pneumonia

Abstract

For children with ambulatory pneumonia, the World Health Organization (WHO) recommends oral amoxicillin (15 mg/kg of body weight/dose) thrice daily (t.i.d.) or oral cotrimoxazole (4 mg of trimethoprim/kg/dose) twice daily (b.i.d.). The more frequent amoxicillin dosing may lead to compliance problems. To compare the pharmacokinetics and levels of amoxicillin in plasma in the current WHO acute respiratory infection recommendations with the 25-mg/kg/dose b.i.d. regimen, we performed a two-group parallel study of 66 children ages 3 to 59 months with pneumonia. Amoxicillin was given orally at 25 mg/kg/dose b.i.d. or 15 mg/kg/dose t.i.d. Amoxicillin concentrations were determined by high-performance liquid chromatography after the first dose on days 1 and 3. After the first dose on day 1, the mean area under the concentration-time curve (AUC) for amoxicillin after the 25-mg/kg dose was 54.7 versus 24.9 micro g. h/ml after the 15-mg/kg dose. After the first dose on day 3, the mean AUC was 44.1 versus 28.5 micro g. h/ml. All but two children had plasma amoxicillin concentrations above 0.5 micro g/ml for >50% of the dose interval on both days. Six children on day 1 and five children on day 3 had concentrations above 1.0 micro g/ml for <50% of the dose interval. On day 1, 16 of 27 children in the b.i.d. group and 11 of 26 children in the t.i.d. group had concentrations that were above 2.0 micro g/ml for <50% of the dose interval, and on day 3, 18 of 31 children in the b.i.d. group and 8 of 31 children in the t.i.d. group had concentrations that were above 2.0 micro g/ml for <50% of the dose interval. Amoxicillin b.i.d. is a feasible alternative for t.i.d. dosing. To lengthen the time above the MIC at higher concentration levels, a 30- to 40-mg/kg/dose b.i.d. should be considered instead of the 25 mg/kg/dose used in this study.

FIG. 1.

Means (± 95% CI) of plasma amoxicillin concentrations versus time in children after the first dose on day 1 and day 3 of treatment. The children were treated with either 15 mg/kg/dose t.i.d. (filled circles) (n = 34) or 25 mg/kg/dose b.i.d. (open circles) (n = 32) administered orally.

FIG. 2.

Percentage of the dose interval at which the plasma amoxicillin concentration remained above a predetermined level of 0.5, 1.0, or 2.0 μg/ml after the first dose on day 1 and day 3 of treatment. Amoxicillin was administered orally at 15 mg/kg/dose t.i.d. (filled circles) (n = 34) or 25 mg/kg/dose b.i.d. (open circles) (n = 32). The 50 to 60% dose interval is indicated by shading.