Amikacin Therapy in Newborns

Aminoglycosides, including amikacin, are known for their potent activity against bacteria that cause sepsis in newborn foals. Dosage protocols for aminoglycosides have been extensively studied in humans, and conventional dosing at eight- to 12-hour intervals is now giving way to high-dose, once-daily administration. Human studies have shown that amikacin is more effective and less toxic to the kidneys when given this way. Researchers from the University of California, Davis, School of Veterinary Medicine are investigating whether high-dose, once-daily administration of aminoglycosides works well in horses, too. Gary Magdesian, DVM, Dipl. ACVIM, ACVP, ACVECC, and colleagues recently took the first step in answering this question by administering high-dose amikacin to newborn foals once a day with close monitoring of drug distribution and elimination.

Seven healthy foals less than one day old were started on amikacin at 21 mg/kg body weight given IV once a day for 10 days (compared to a traditional regimen of 6.6 mg/kg IV every eight to 12 hours). Blood samples were collected before drug administration, repeatedly the first hour, and at various hourly intervals until the next dose. Plasma samples were analyzed for pharmacologic variables such as volume of distribution, half-life of elimination, and clearance. Results were compared for evidence of change as the foals matured.

As expected, high-dose amikacin yielded very high peak plasma levels both right away and one hour after administration. "The higher the peak plasma concentration, the greater the rate and extent of bacterial killing," explains Magdesian.

There was also a significant increase in "area under the curve," or AUC, which is a variable known to positively correlate with increased bactericidal effectiveness of aminoglycosides. AUC was two to four times higher in high-dose foals compared to traditional dosing. As foals aged, there was enhanced clearance of amikacin in the urine compared to younger foals, which indicates maturity of renal function. More importantly, there was no evidence of renal toxicity in any foal.

The authors concluded that high-dose, once-daily amikacin can provide enhanced bactericidal activity. "However," Magdesian cautions, "disease alters the pharmacokinetics of drugs. Therefore, additional studies should be conducted in septic or critically ill foals to confirm these results."

Magdesian's other research projects include studies in neonatal hemodynamics and disease, as well as fluid balance and diarrhea in horses.

Magdesian, K.G.; Wilson, W.D.; Mihalyi, J. American Journal of Veterinary Research, 65 (4): 473-478, 2004.

About the Author

Susan Piscopo, DVM, PhD

Susan Piscopo, DVM, PhD, is a free-lance writer in the biomedical sciences. She practiced veterinary medicine in North Carolina before accepting a fellowship to pursue a PhD in physiology at North Carolina State University. She lives in northern New Jersey with her husband and two sons.

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