Effects of hypoxia and azotaemia on the pharmacokinetics of amikacin in neonatal foals.

The research studies how low oxygen levels (hypoxia) and excess nitrogen in the blood (azotaemia) affect how the antibiotic amikacin works in newborn foals in critical condition. The study shows that these conditions affect how the foals’ bodies clear the antibiotic and how much of it is present in their blood. However, the drug did not reach toxic levels.

Study Design and Findings

The researchers evaluated 20 newborn foals that needed intensive care. The young horses had symptoms of hypoxia, azotaemia, and sepsis. They were given aggressive intravenous therapy with dextrose-supplemented polyionic fluids, oxygen, and nutritional supplements. They also received amikacin.

• The study found no connection between the foals’ sepsis scores or survival rates and how their bodies processed the antibiotic.
• Concurrent hypoxia and azotaemia did significantly affect the pharmacokinetics of amikacin – the process by which the drug is absorbed, distributed, metabolized, and excreted from the body. These conditions led to reduced clearance of the drug, meaning the drug stayed in the body longer, and increased its concentrations in the foals’ blood, although not to toxic levels.
• The issues with serum peak, trough, and clearance values were present when the foals were first admitted and continued throughout the six-day study period.

Implications and Adjustments

• Monitoring the concentration of amikacin in the foals’ blood showed that there was a tendency to underdose the antibiotic, especially in foals receiving intensive fluid therapy. As a result, the dose was increased in 40% of the cases, both in terms of the amount of drug given relative to body weight and the frequency of dosing. This adjustment was made to keep the drug concentration within the target range in the blood.
• Despite these adjustments, there was no evidence of kidney toxicity from the antibiotic, based both on standard lab tests and post-mortem examinations.

Conclusion

The research suggests that conditions such as hypoxia and azotaemia, which are common in critically ill newborn foals, may affect the pharmacokinetics of the antibiotic amikacin. Regular monitoring and dose adjustments may be necessary to maintain therapeutic drug levels and to avoid the risk of toxicity. However, more extensive studies are needed to confirm these findings and to better understand how these conditions affect drug pharmacokinetics in newborn foals.