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Pharmacokinetics of meloxicam administered orally to rabbits (Oryctolagus cuniculus) for 29 days
Katie W Delk1, James W Carpenter, Butch KuKanich
1Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.
Objective:
To determine the pharmacokinetics and safety of meloxicam in rabbits when administered orally for 29 days.
Animals:
6 healthy rabbits.
Procedures:
Meloxicam (1.0 mg/kg, PO, q 24 h) was administered to rabbits for 29 days. Blood was collected immediately before (time 0) and 2, 4, 6, 8, and 24 hours after drug administration on days 1, 8, 15, 22, and 29 to evaluate the pharmacokinetics of meloxicam. On day 30, an additional sample was collected 36 hours after treatment. Plasma meloxicam concentrations were quantified with liquid chromatography-mass spectrometry, and noncompartmental pharmacokinetic analysis was performed. Weekly plasma biochemical analyses were performed to evaluate any adverse physiologic effects. Rabbits were euthanatized for necropsy on day 31.
Results:
Mean ± SD peak plasma concentrations of meloxicam after administration of doses 1, 8, 15, 22, and 29 were 0.67 ± 0.19 μg/mL, 0.81 ± 0.21 μg/mL, 1.00 ± 0.31 μg/mL, 1.00 ± 0.29 μg/mL, and 1.07 ± 0.19 μg/mL, respectively; these concentrations did not differ significantly among doses 8 through 29. Results of plasma biochemical analyses were within reference ranges at all time points evaluated. Gross necropsy and histologic examination of tissues revealed no clinically relevant findings.
Conclusions And Clinical Relevance:
Plasma concentrations of meloxicam for rabbits in the present study were similar to those previously reported in rabbits that received 1. 0 mg of meloxicam/kg, PO every 24 hours, for 5 days. Results suggested that a dosage of 1. 0 mg/kg, PO, every 24 hours for up to 29 days may be safe for use in healthy rabbits.
Insights
This study found that oral meloxicam at 1.0 mg/kg daily for 29 days is safe and well-tolerated in healthy rabbits. Plasma meloxicam concentrations remained consistent and within safe limits throughout the study period.
Area of Science:
- Veterinary Pharmacology
- Animal Toxicology
- Pharmacokinetics
Background:
- Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) used for pain management.
- Limited pharmacokinetic and safety data exist for long-term oral meloxicam administration in rabbits.
Purpose of the Study:
- To assess the pharmacokinetics and safety profile of daily oral meloxicam administration in healthy rabbits over a 29-day period.
- To establish safe dosage guidelines for meloxicam in this species.
Main Methods:
- Six healthy rabbits received oral meloxicam (1.0 mg/kg) once daily for 29 days.
- Plasma meloxicam concentrations were measured at multiple time points post-administration on various days.
- Plasma biochemical analyses and necropsy were performed to evaluate safety and adverse effects.
Main Results:
- Peak plasma meloxicam concentrations increased initially but stabilized from day 8 onwards.
- All plasma biochemical analyses remained within normal reference ranges throughout the study.
- No significant adverse findings were observed during gross necropsy or histologic examination.
Conclusions:
- Oral meloxicam at 1.0 mg/kg/day for 29 days demonstrated predictable pharmacokinetics in rabbits.
- The drug was found to be safe and well-tolerated in healthy rabbits with no observed adverse physiological effects.
