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Fever and associated changes in glomerular filtration rate erase anticipated diurnal variations in aminoglycoside
F Fauvelle1, P Perrin, L Belfayol
1Laboratory of Clinical Pharmacy, Montfermeil Hospital, France.
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.
Insights
Administering netilmicin at 10 a.m. or 10 p.m. yielded similar serum concentrations and pharmacokinetic profiles in patients with severe infections. This finding supports flexible dosing schedules for netilmicin when given once daily.
Area of Science:
- Pharmacology
- Clinical Pharmacy
- Infectious Diseases
Background:
- Severe infections require effective antibiotic therapy.
- Aminoglycosides like netilmicin are crucial for treating serious bacterial infections.
- Optimizing antibiotic dosing is essential for maximizing efficacy and minimizing toxicity.
Purpose of the Study:
- To investigate the impact of once-daily intravenous netilmicin administration time (10 a.m. vs. 10 p.m.) on serum concentrations and pharmacokinetic parameters in patients with severe infections.
- To determine if the timing of netilmicin dosing influences its therapeutic levels and disposition in critically ill patients.
Main Methods:
- A prospective study involving 43 patients with severe infections, divided into two groups.
- Group I received netilmicin (4.5 mg/kg lean body weight) intravenously at 10 a.m.; Group II received it at 10 p.m.
- Serum peak and trough concentrations, half-life, volume of distribution, and total clearance were measured and compared between groups.
Main Results:
- No statistically significant differences were observed in serum peak (12.9 vs. 12.8 mg/L) or trough (0.7 vs. 0.8 mg/L) concentrations between the 10 a.m. and 10 p.m. administration groups.
- Key pharmacokinetic parameters, including half-life (5.0 vs. 4.9 h), volume of distribution (0.32 vs. 0.35 L/kg), and total clearance (0.920 vs. 1.015 ml/min/kg), were similar in both groups.
- The time of administration did not significantly influence netilmicin levels or pharmacokinetic behavior.
Conclusions:
- Once-daily intravenous administration of netilmicin at either 10 a.m. or 10 p.m. results in comparable serum concentrations and pharmacokinetic profiles in patients with severe infections.
- The timing of netilmicin dosing does not appear to be a critical factor for achieving therapeutic efficacy and safety in this patient population when administered on a once-daily schedule.
- These findings suggest flexibility in scheduling netilmicin administration to accommodate clinical convenience without compromising its pharmacokinetic performance.