Chronobiology and chronotoxicology of antibiotics and aminoglycosides.

Few investigators have examined the circadian variation in the symptom intensity of infectious diseases. Seasonal patterns in a variety of infectious are well know. Less appreciated are the circadian patterns in the symptom expression of infections. Studies indicate that fever which accompanies the common cold peaks at 4 p.m., and this is in agreement with other studies indicating that the elevation of body temperature, fever, due to bacterial infections is higher in the evening while that due to viral infections is more likely in the morning. Animal and human studies reveal also administration-time-dependent differences in the pharmacokinetics and toxicity of antimicrobial agents. This is particularly true for the aminoglycosides, as their nephrotoxicity is greatest when administered during the resting period of laboratory animals and human beings. Food intake and low urinary pH has been found to be protective of the toxicity of aminoglycosides at this time of the day. Knowledge of the administration-time-dependence of aminoglycosides and the underlying mechanisms can be used to develop once-a-day formulations that are significantly less toxic, in particular to the kidney, in patients who require around-the-clock antimicrobial therapy.