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

Abstract

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.

Fungal diversity and drug susceptibility of the oral mycobiome of domestic dogs

“…But it is still important to note the elevated MIC values and evidence for multi-drug resistance in these commensals (Figure 4A). These data can also help assess the risk and predicted efficacy of using antifungal drugs in dogs for effective treatment, including prophylaxis and longterm treatments (45)(46)(47)(48)(49).…”

Two doses of subcutaneous methadone for postoperative analgesia in dogs undergoing tibial plateau levelling osteotomies

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Correlation of opioid antinociception and hypothermia in dogs—An animal welfare refinement

“…For example, methadone is approved for canine use in some countries at a dosage of 0.5–1 mg/kg IV, IM, SC, but some veterinarians suggest that this dose is too high in dogs. Clinical trials conducted by our research team demonstrated methadone 0.5 mg/kg SC q4 h provided effective and well‐tolerated analgesia in dogs undergoing soft tissue surgery, n = 33 total dogs (Bieberly et al., 2022; KuKanich et al., 2020).…”