Background: To characterize urinary isolates, the Clinical and Laboratory Standards Institute (CLSI) uses an amoxicillin breakpoint for cats based on plasma (not urine) drug concentrations (≤0.25 μg/mL), but a urine-specific breakpoint for dogs exists (≤8 μg/mL). Objectives: To measure urine concentrations of amoxicillin and clavulanate after PO administration of amoxicillin-clavulanate to cats, and to suggest updated urine-specific susceptibility breakpoints for PO amoxicillin and amoxicillin-clavulanate in cats. Animals: Eleven healthy purpose-bred cats. Methods: Cats were given 3 62.5 mg doses of amoxicillin-clavulanate PO q12h. After the third dose, urine was collected over 28 hours, recording urination time and volume. At least 3 urine samples were collected per cat. Liquid chromatography with mass spectrometry was used to determine the urine concentrations of amoxicillin and clavulanate. Results: Amoxicillin concentrations were >8 μg/mL in all urine samples collected within 12 hours after administration (range, 31.6-1351 μg/mL), with means of 929 μg/mL (0-6 hours) and 532 μg/mL (6-12 hours). The mean half-life of amoxicillin in urine was 1.99 hours, and mean recovery was 30%. Clavulanate was detected in all urine samples, with mean half-life of 2.17 hours. Conclusions and Clinical Importance: Orally administered amoxicillin-clavulanate resulted in urine amoxicillin concentrations above the cutoff (8 μg/mL) for wild-type Escherichia coli in all cats. Because urine-specific susceptibility testing breakpoints can be determined using urine concentrations, this information should allow new CLSI uropathogen susceptibility breakpoints for amoxicillin and amoxicillinclavulanate in healthy cats, increasing the urine breakpoint from ≤0.25 to ≤8 μg/mL.

OBJECTIVE To assess the pharmacokinetics, clinical efficacy, and adverse effects of injectable methadone with the pharmacokinetic enhancer fluconazole (methadone-fluconazole), compared with the standard formulation of injectable methadone, in dogs after ovariohysterectomy. We hypothesized that 2 doses of methadone-fluconazole would provide 24 hours of postoperative analgesia. ANIMALS 3 purpose-bred dogs (pharmacokinetic preliminary study) and 42 female dogs from local shelters (clinical trial) were included. PROCEDURES Pharmacokinetics were preliminarily determined. Clinical trial client-owned dogs were blocked by body weight into treatment groups: standard methadone group (methadone standard formulation, 0.5 mg/kg, SC, q 4 h; n = 20) or methadone-fluconazole group (0.5 mg/kg methadone with 2.5 mg/kg fluconazole, SC, repeated once at 6 h; n = 22). All dogs also received acepromazine, propofol, and isoflurane. Surgeries were performed by experienced surgeons, and dogs were monitored perioperatively using the Glasgow Composite Measure Pain Scale–Short Form (CMPS-SF) and sedation scales. Evaluators were masked to treatment. RESULTS Findings from pharmacokinetic preliminary studies supported that 2 doses of methadone-fluconazole provide 24 hours of drug exposure. The clinical trial had no significant differences in treatment failures or postoperative CMPS-SF scores between treatments. One dog (methadone-fluconazole group) had CMPS-SF > 6 and received rescue analgesia. All dogs had moderate sedation or less by 1 hour (methadone-fluconazole group) or 4 hours (standard methadone group) postoperatively. Sedation was completely resolved in all dogs the day after surgery. CLINICAL RELEVANCE Methadone-fluconazole with twice-daily administration was well tolerated and provided effective postoperative analgesia for dogs undergoing ovariohysterectomy. Clinical compliance and postoperative pain control may improve with an effective twice-daily formulation.