EFFECT OF ROUTE OF ADMINISTRATION AND AGE ON THE PHARMACOKINETICS OF AMIKACIN ADMINISTERED BY THE INTRAVENOUS AND INTRAOSSEOUS ROUTES TO 3-DAY-OLD AND 5-DAY-OLD FOALS

The suitability of the intraosseous (i.o.) route for drug administration to equine neonates was evaluated in a study comparing the pharmacokinetics of amikacin administered by the i.o. and intravenous (i.v.) routes. Using a cross-over study design amikacin sulphate (7 mg/kg bwt) was administered i.o. or i.v. to 6 healthy foals at 3 and 5 days of age. Amikacin was instantaneously and completely absorbed after i.o. administration, achieving a mean +/- sd peak concentration (34.17 +/- 3.54 mu g/ml) in the first sample collected 3 min after administration which was not significantly different from the mean +/- sd peak concentration (32.92 +/- 2.63 mu g/ml) achieved after i.v. administration. The plasma amikacin concentration-time profiles for the i.o. and i.v. routes were not different and both were appropriately described by a 2-compartment open pharmacokinetic model. No significant differences attributable to route of administration were found in values for the major pharmacokinetic variables. The degree of inter-individual variation in values for indices of clearance was considerably greater than the degree of variation attributable to age. Despite this, values for body clearance (CIB) were significantly higher (P < 0.05) and values for area under the plasma amikacin concentration time curve (AUC) and concentration of amikacin in plasma at 8 h [Cp(8h)] were significantly lower in 5- than in 3-day-old foals, indicating that amikacin was more rapidly cleared by the older foals. Technical difficulties were not encountered during i.o. needle placement in the medial aspect of the proximal tibia. Mild diffuse soft tissue swelling which developed at the i.o. site resolved completely within 1-2 months. Radiographs demonstrated a bony healing process with minor periosteal and endosteal proliferation. The i.o. route appears to be safe, practical and effective for rapid delivery of amikacin to neonatal foals.