[Chronotoxicity of amikacin]

Area of Science:

• Pharmacology
• Chronobiology
• Toxicology

Background:

• Antibiotic efficacy and toxicity can be influenced by biological rhythms.
• Understanding circadian variations is crucial for optimizing drug administration.
• Amikacin is a widely used aminoglycoside antibiotic.

Purpose of the Study:

• To investigate the impact of circadian rhythms and seasonal changes on amikacin toxicity in mice.
• To determine if the timing of amikacin administration affects its acute toxicity.
• To explore potential chronotherapeutic strategies for amikacin use.

Main Methods:

• Female mice received a single lethal dose of amikacin (1.6-1.9 g/kg) via intraperitoneal injection.
• Injections were administered at four different circadian time points (8h, 14h, 20h, 2h).
• Experiments were conducted during two distinct seasons (late autumn/early winter and spring).
• Mortality was recorded daily for seven days post-injection.

Main Results:

• Mortality rates from amikacin toxicity varied significantly based on administration time and season.
• In autumn/winter, toxicity peaked at 2h (60% mortality) and was lowest at 14h (47.75%).
• In spring, the pattern reversed, with higher toxicity at 14h (36.6%) and lower at 2h (23.3%).

Conclusions:

• Acute amikacin toxicity in mice exhibits significant circadian and seasonal variations.
• These findings highlight the importance of chronopharmacology in antibiotic treatment.
• Further research is warranted to translate these findings into optimized clinical antibiotic use in humans.