Fever and associated changes in glomerular filtration rate erase anticipated diurnal variations in aminoglycoside pharmacokinetics.
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.
Fauvelle
F
F
Laboratory of Clinical Pharmacy, Montfermeil Hospital, France.
Perrin
P
P
Belfayol
L
L
Boukari
M
M
Cherrier
P
P
Bosio
A M
AM
Tod
M
M
Coulaud
J M
JM
Petitjean
O
O
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001499:Bayes Theorem; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D005334:Fever / Q000378:metabolism* / Q000503:physiopathology; D016231:Fluorescence Polarization Immunoassay; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009428:Netilmicin / Q000008:administration & dosage / Q000493:pharmacokinetics
D000900:Anti-Bacterial Agents; D009428:Netilmicin