J vet Pharmacol Therap. 2020;00:1–6. wileyonlinelibrary.com/journal/jvp | 1 © 2020 John Wiley & Sons Ltd 1 | INTRODUCTION Cefuroxime axetil (C 20 H 22 N 4 O 10 S) (CEFa) is an acetoxyethyl ester prodrug of cefuroxime (C 16 H 16 N 4 O 8 S) (CEF) appropriate for oral administration. It is hydrolyzed by esterases in the gastrointestinal tract to the active CEF, which is absorbed into the systemic circula- tion (Perry & Brogden 1996). Cefuroxime has a broad spectrum of antimicrobial activity. It is active against many gram-positive (e.g., Staphylococci and Streptococci), gram-negative (Enterobacteriaceae), and some Received: 5 September 2019 | Revised: 15 January 2020 | Accepted: 8 February 2020 DOI: 10.1111/jvp.12854 ORIGINAL ARTICLE Effect of food on the pharmacokinetics of oral cefuroxime axetil in dogs Gabriela A. Albarellos 1 | Sabrina M. Passini 1 | Martín P. Lupi 1 | Silvia Aramayona 1 | Paula M. Lorenzini 1 | Laura Montoya 1 | Maria F. Landoni 2 1 Facultad de Ciencias Veterinarias, Cátedra de Farmacología, Universidad de Buenos Aires, Buenos Aires, Argentina 2 Facultad de Ciencias Veterinarias, Cátedra de Farmacología, Universidad Nacional de La Plata, Buenos Aires, Argentina Correspondence Gabriela A. Albarellos. Facultad de Ciencias Veterinarias, Cátedra de Farmacología, Universidad de Buenos Aires, Chorroarín 280 (1427). Buenos Aires, Argentina. Email: albarell@fvet.uba.ar Funding information Secretaria de Ciencia y Tecnica, Universidad de Buenos Aires, Grant/Award Number: UBACYT 2018-2020 20020170100574BA Abstract Cefuroxime axetil pharmacokinetic profile was investigated in 12 Beagle dogs after single intravenous and oral administration of tablets or suspension at a dose of 20 mg/ kg, under both fasting and fed conditions. A three-period, three-treatment crossover study (IV, PO under fasting and fed condition) was applied. Blood samples were with- drawn at predetermined times over a 12-hr period. Cefuroxime plasma concentra- tions were determined by HPLC. Data were analyzed by compartmental analysis. No statistically significant differences were observed between formulations and feeding conditions on PK parameters. Independently of the feeding condition, absorption of cefuroxime axetil after tablet administration was low and erratic. The drug has been quantified in plasma in 3 out of 6 and 5 out of 6 dogs in the fasted and fed groups. For this formulation, the bioavailability (F), peak plasma concentration (C max ), and area under the concentration–time curve (AUC) of cefuroxime axetil were significantly en- hanced (p < .05) by the concomitant ingestion of food (32.97 ± 13.47–14.08 ± 7.79%, 6.30 ± 2.62–2.74 ± 0.66 µg/ml, and 15.75 ± 3.98–7.82 ± 2.76 µg.hr/ml for F, C max, and AUC in fed and fasted dogs, respectively), while for cefuroxime axetil suspension, feeding conditions affected only the rate of absorption, as reflected by the significantly shorter absorption half-life (T ½(a) ) and time to peak concentration (T max ) (0.55 ± 0.27– 1.15 ± 0.19 hr and 1.21 ± 0.22–1.70 ± 0.30 for T ½(a) and T max in fed and fasted dogs, respectively). For cefuroxime axetil tablets, T > MIC (≤1 µg/ml) was <2 hr in fasted and ≈4 hr in fed animals, and for cefuroxime axetil suspension, T > MIC (≤1 µg/ml) was ≈5 hr and for T >MIC (≤4 µg/ml) was ≈2.5 hr for fasted and fed dogs, respectively. Cefuroxime axetil as a suspension formulation seems to be a better option than tablets. However, its short permanence in plasma could reduce its clinical usefulness in dogs. KEYWORDS antimicrobials, cefuroxime, cephalosporins, dogs, pharmacokinetics