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 administrati on to equine neonates was evaluated in a study comparing the pharmacok inetics of amikacin administered by the i.o. and intravenous (i.v.) ro utes. 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 ag e. Amikacin was instantaneously and completely absorbed after i.o. adm inistration, achieving a mean +/- sd peak concentration (34.17 +/- 3.5 4 mu g/ml) in the first sample collected 3 min after administration wh ich was not significantly different from the mean +/- sd peak concentr ation (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. rou tes were not different and both were appropriately described by a 2-co mpartment open pharmacokinetic model. No significant differences attri butable 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 deg ree of variation attributable to age. Despite this, values for body cl earance (CIB) were significantly higher (P < 0.05) and values for area under the plasma amikacin concentration time curve (AUC) and concentr ation of amikacin in plasma at 8 h [Cp(8h)] were significantly lower i n 5- than in 3-day-old foals, indicating that amikacin was more rapidl y cleared by the older foals. Technical difficulties were not encounte red during i.o. needle placement in the medial aspect of the proximal tibia. Mild diffuse soft tissue swelling which developed at the i.o. s ite 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.