Pharmacokinetics, Milk Residues, and Toxicological Evaluation of a Single High Dose of Meloxicam Administered at 30 mg/kg per os to Lactating Dairy Cattle

SIMPLE SUMMARY: Pain control is a major concern for cattle producers, consumers, and veterinarians. There are currently no analgesic drugs labeled for pain control in lactating dairy cattle in the United States. However, veterinarians are permitted to use analgesic drugs approved in other species in an extra-label manner, but the safety profile of these formulations, especially non-steroidal anti-inflammatory drugs (NSAIDs) administered at high doses, is lacking. NSAID toxicosis is rarely reported in cattle, and the risk level for meloxicam is unknown. This report examined the pharmacokinetics, milk residues, and toxicologic outcomes of a single 30 mg/kg oral dose of meloxicam in lactating dairy cattle. ABSTRACT: Adverse effects associated with overdose of NSAIDs are rarely reported in cattle, and the risk level is unknown. If high doses of NSAIDs can be safely administered to cattle, this may provide a longer duration of analgesia than using current doses where repeated administration is not practical. Meloxicam was administered to 5 mid-lactation Holstein dairy cows orally at 30 mg/kg, which is 30 times higher than the recommended 1 mg/kg oral dose. Plasma and milk meloxicam concentrations were determined using high-pressure liquid chromatography with mass spectroscopy (HPLC-MS). Pharmacokinetic analysis was performed by using noncompartmental analysis. The geometric mean maximum plasma concentration (C(max)) was 91.06 µg/mL at 19.71 h (T(max)), and the terminal elimination half-life (T(1/2)) was 13.79 h. The geometric mean maximum milk concentration was 33.43 µg/mL at 23.74 h, with a terminal elimination half-life of 12.23 h. A thorough investigation into the potential adverse effects of a meloxicam overdose was performed, with no significant abnormalities reported. The cows were humanely euthanized at 10 d after the treatment, and no gross or histologic lesions were identified. As expected, significantly higher plasma and milk concentrations were attained after the administration of 30 mg/kg meloxicam with similar half-lives to previously published reports. However, no identifiable adverse effects were observed with a drug dose 30 times greater than the industry uses within 10 days of treatment. More research is needed to determine the tissue withdrawal period, safety, and efficacy of meloxicam after a dose of this magnitude in dairy cattle.