AMOXICILLIN PHARMACOKINETICS IN PRETERM INFANTS WITH GESTATIONAL AGESOF LESS-THAN 32 WEEKS

The multiple-dose pharmacokinetics of amoxicillin (AM [administered tw ice daily in a 25-mg/kg of body weight intravenous dose]) in 17 preter m infants (11 males; gestational age, 29 +/- 1.9 weeks; birth weight, 1,175 +/- 278 g) were evaluated on day 3 of life, Blood samples were c ollected from an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h aft er the intravenous dose, A high-performance liquid chromatography meth od was used to determine AM concentrations in serum, AM pharmacokineti cs followed a one-compartment open model, The glomerular filtration ra tes of all patients were simultaneously studied by means of the 24-h c ontinuous inulin infusion technique, The elimination half-life, appare nt volume of distribution, and total body clearance of AM (mean +/- st andard deviation) were 6.7 +/- 1.7 h, 584 +/- 173 ml, and 62.4 +/- 23. 3 ml/h, respectively, The mean (+/- standard deviation) AM peak and tr ough levels were 53.6 +/- 9.1 and 16.0 +/- 4.9 mg/liter, respectively, All infants had a serum trough level above 5 mg/liter, The total body clearance and apparent volume of distribution of AM and the clearance of inulin increased significantly with increasing gestational age, Th e total body clearance of AM (1.0 +/- 0.4 ml/min) and the clearance of inulin (1.0 +/- 0.3 ml/min) were similar, The total body clearance of AM increased significantly with increasing clearance of inulin, We co nclude that an AM dose of 25 mg/kg every 12 h given to preterm infants in the first week of life with gestational ages of less than 32 weeks results in serum levels well above the MIC for major microorganisms i nvolved in neonatal infections,