Fever and associated changes in glomerular filtration rate erase anticipated diurnal variations in aminoglycoside pharmacokinetics

Abstract

Netilmicin (4.5 mg/kg of lean body weight) was administered intravenously once every 24 h at 10 a.m. to 23 patients (group I) and at 10 p.m. to 20 patients (group II) with severe infection. No significant differences (P > 0.05) in peak and trough concentrations in serum were found between groups I and II (peak, 12.9 +/- 3.7 versus 12.8 +/- 4.4 mg/liter, respectively; trough, 0.7 +/- 0.6 versus 0.8 +/- 0.6 mg/liter, respectively [mean +/- standard deviation]). Pharmacokinetic parameters (half-life [5.0 +/- 2.2 versus 4.9 +/- 1.8 h], volume of distribution [0.32 +/- 0.04 versus 0.35 +/- 0.06 liter/kg], and total clearance [0.920 +/- 0.417 versus 1.015 +/- 0.546 ml/min/kg]) were similar in the two groups and not influenced by the time of administration. These data suggest that, in the once-daily schedule, 10 a.m. or 10 p.m. administration had no influence on netilmicin levels in serum and pharmacokinetic parameters in these ill febrile patients.