Abstract
Background:
Owner medication compliance with the Clinician's prescription can, among other factors, influence the patient's outcome. It has been postulated that extending the dosing interval (DI) may improve medication compliance. Hence, an oral long-acting (LA) preparation of enrofloxacin as minispheres was developed.

Aim:
To develop a tasteless LA preparation of enrofloxacin as minispheres, capable of achieving Cmax and AUC values equal to or greater than those of the reference flavored tablet. Additionally, to facilitate dosing of the experimental minispheres, the dose was concealed in either pathé or cream cheese morsels.

Methods:
The pharmacokinetics (PK) of the reference preparation and the experimental minispheres, dosing them as two 10 mg/kg/day or 15 mg/kg once, respectively, were defined. The HCl·2H2O solvate of enrofloxacin was utilized together with pH-sensitive multilayer polymers to manufacture the minispheres. To further facilitate dosing, the minispheres were concealed in pathé or cream cheese morsels. HPLC analysis allowed the determination of the plasma concentrations of the reference enrofloxacin for both preparations.

Results:
The Cmax, AUC0-48 were highest for the minispheres concealed in pathé, followed by morsels of cream cheese. When assessing key PK/PD ratios for enrofloxacin and considering the breakpoint of 0.5 µg/mL, i.e., Cmax/MIC0.5 ≥ 10-12 and AUC0-24/MIC0.5 ≥ 125, only the experimental minispheres concealed in cream cheese or pâté morsels exceeded the referred ratios. Predictably, minispheres showed a larger mean residence time. Hence, a DI of 48 h is proposed for the experimental minispheres.

Conclusion:
Given the PK/PD relationships obtained with the experimental minispheres, a 15 mg/kg dose every 48 hours (15 mg/kg) is recommended. This prototype is presented to the veterinary clinical community for further evaluation to assess clinical efficacy and medication compliance performance.

Key words: Medication compliance; Dogs; Enrofloxacin; Long-acting; PK/PD.