Long-acting injectable methadone (methadone-fluconazole) provides safe and effective postoperative analgesia in a randomized clinical trial for dogs undergoing soft tissue surgery.

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.

Evaluation of urine concentrations of amoxicillin and clavulanate in cats.

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 amoxicillin-clavulanate in healthy cats, increasing the urine breakpoint from ≤0.25 to ≤8 µg/mL.