Suitability of prolonged meloxicam treatment in mice seems limited due to unfavorable pharmacokinetics, side effects, and impact on home-cage behaviors

Meloxicam is commonly used for analgesia, but no preparation approved specifically for use in mice. Here, we determined plasma concentrations, safety, and impact on home-cage behaviors for subcutaneous injection (5 mg/kg) and oral self-intake (sweetened drinking water, 20 mg/kg/24h, 5 days) for C57BL/6J mice (n = 21/sex). After injection, plasma concentrations measured by LC-MS/MS were higher in females (2h) and remained within an estimated therapeutic range (390-911 ng/mL) for up to 6h. T_1/2 was 2.32 h. Despite acceptance, plasma levels fluctuated strongly during oral self-intake. Side effects comprised reduced grip strength and increased vocalization (Irwin test), increased clinical score values (females, oral treatment) with two individuals reaching humane endpoint, increase in body temperature, body weight drop, decreased wheel-running activity, increased burrowing latency (males), and prolonged grooming activity (females). Grimace scale, nesting activity and plasma corticosterone remained unaffected. Red blood profile parameters and ALT were decreased and Ca²⁺ and Cl^- concentrations elevated. Histopathological analysis revealed inflammatory cells and hyperplasia in stomach and jejunum. In view of the unfavorable pharmacokinetics, meloxicam treatment via the drinking water is unsuitable in mice. The limited tolerability make prolonged treatment with the doses studied appear inappropriate.