Netilmicin and gentamicin multidose kinetics in normal subjects

Area of Science:

• Pharmacokinetics
• Clinical Pharmacology
• Drug Metabolism and Elimination

Background:

• Aminoglycosides like gentamicin and netilmicin are crucial antibiotics.
• Understanding their long-term kinetic behavior and safety is essential for effective clinical use.

Purpose of the Study:

• To compare the multidose pharmacokinetics of netilmicin and gentamicin.
• To evaluate the safety profiles of these two aminoglycosides over a 10-day treatment period.

Main Methods:

• A randomized, double-blind trial involving 20 healthy subjects.
• Administration of 1.7 mg/kg gentamicin or netilmicin every 8 hours for 10 days (28 doses).
• Analysis of plasma and urine samples to determine drug concentrations and elimination rates.

Main Results:

• Multidose kinetics were similar, except for terminal plasma half-life (t 1/2) and volume of distribution (Vdss).
• Netilmicin exhibited a longer t 1/2 (156 hr vs. 94 hr) and larger Vdss (1072 ml/kg vs. 450 ml/kg) compared to gentamicin.
• Aminoglycosides remained detectable in plasma and urine for at least 6 days post-treatment, with no auditory, vestibular, or renal toxicity observed.

Conclusions:

• Netilmicin and gentamicin share similar pharmacokinetic characteristics, but with notable differences in terminal elimination and distribution.
• The presence of a deep tissue compartment suggests complex kinetic processes for these aminoglycosides.
• Both drugs demonstrated a favorable safety profile in healthy subjects during this study.