Pharmacokinetic studies of meloxicam following oral and transdermal administration in Beagle dogs

Abstract

Aim:The potential for topical delivery of meloxicam was investigated by examining its pharmacokinetic profiles in plasma and synovial fluid following oral and transdermal administration in Beagle dogs. Methods: The experiment was a two-period, crossover design using 6 Beagle dogs. Meloxicam tablets were administered orally at a dose of 0.31 mg/kg, and meloxicam gel was administered transdermally at a dose of 1.25 mg/kg. Drug concentrations in plasma and synovial fluid were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The pharmacokinetic parameters were calculated using the Topfit 2.0 program. Results: The pharmacokinetic results showed that AUC 0-t (23.9±8.26 µg·h·mL -1 ) in plasma after oral administration was significantly higher than after transdermal delivery (1.00±0.43 µg·h·mL -1 ). In contrast, the ratio of the average concentration in synovial fluid to that in plasma following transdermal administration was higher than that for an oral delivery. The synovial fluid concentration in the treated leg was much higher than that in the untreated leg, whereas the synovial fluid concentration in the untreated leg was similar to the plasma concentration. Conclusion: The high concentration ratio of synovial fluid to plasma indicates direct penetration of meloxicam following topical administration to the target tissue. This finding is further supported by the differences observed in meloxicam concentrations in synovial fluid in the treated and untreated joints at the same time point. Our results suggest that transdermal delivery of meloxicam is a promising method for decreasing its adverse systemic effects.

Treatment of meloxicam overdose in a dog via therapeutic plasma exchange

“…Meloxicam is a slightly preferential inhibitor of COX‐2 at therapeutic doses . Inhibition of COX‐2 prevents the production of certain inflammatory prostaglandins from the arachidonic acid pathway, which are induced by inflammatory stimuli in pathological conditions .…”

“…Meloxicam is a slightly preferential inhibitor of COX-2 at therapeutic doses. [3][4][5] Inhibition of COX-2 prevents the production of certain inflammatory prostaglandins from the arachidonic acid pathway, which are induced by inflammatory stimuli in pathological conditions. 31 COX-1 is referred to as a constitutive or "housekeeping" enzyme and occurs naturally in many tissues of the body at a fairly constant concentration.…”

“…1,2 Meloxicam is a preferential cyclooxygenase type 2 (COX-2) inhibitor in the enolic acid class of NSAIDs with analgesic, anti-inflammatory, and antipyretic properties. [2][3][4][5][6][7] At higher doses the specificity for the COX-2 isoenzyme is reduced. 3,8,9 Meloxicam is currently registered for veterinary use in dogs in the United States, Canada, Europe, and Australia and is available in oral (1.5 mg/mL) and parenteral (5 mg/mL) veterinary formulations and human prescription oral tablets (7.5 and 15 mg).…”

"SonoBandage" a transdermal ultrasound drug delivery system for peripheral neuropathy

“…Between these studies and studies demonstrating safety of transdermal NSAID delivery in animals (Yuan et al, 2009), the groundwork for clinical research involving the delivery of NSAIDs to treat peripheral nerve pain appears complete. The next logical step for this work is to take the results of these works, estimate dose transfer levels, and titrate the dose in the SonoBandage to ensure the greatest area of effective treatment concentrations.…”

Strategies for meloxicam delivery to and across the skin: a review

“…Pharmacokinetic characteristics in plasma and synovial fluid were studied after administration of MX by the oral and transdermal route in beagle dogs. The higher drug level in synovial fluid than plasma suggested MX was directly delivered to the site of administration, which demonstrated that drug delivery of MX via skin had great potential to reduce the systemic adverse effects (Yuan et al, 2009). The pharmacokinetic profiles were evaluated by applying 0.5 g MX gel on rat skin, which reached the highest plasma concentration (C max ) of 48.48 ± 6.57 mg/ml at 2 h (T max ) (Gupta et al, 2002).…”