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• W2900932809 abstract "Prescription and OTC non-steroidal anti-inflammatory drugs (NSAIDs) are ubiquitous treatments for pain and inflammation; however, oral administration of these drugs may produce gastrointestinal (GI) side effects. Transdermal (TD) administration of NSAIDs circumvents these adverse events by avoiding the GI tract and, presumably, achieves regional drug levels of therapeutic effect and thereby, fewer off-target complications.A drug quantification method was developed for ibuprofen and celecoxib in canine plasma and synovial fluid using liquid chromatography and mass spectrometry. This method was employed to evaluate the penetrance of ibuprofen and celecoxib topical formulations in dogs. Effectiveness of these topical NSAID formulations was compared to the equivalent oral drug concentration in a canine sodium-urate model of acute joint inflammation. In this model, pain was quantified using a modified Canine Brief Pain Inventory questionnaire and regional inflammation using joint caliper measurements; the significance of intervention was evaluated using linear mixed models for repeated measures along with Bonferroni corrections.After seven days of chronic topical administration, Delivra™ (DEL) formulations of ibuprofen and celecoxib generated serum levels of 2.9µg/mL and 220ng/mL and synovial fluid levels of 1.8 µg/mL and 203 ng/mL (respectively). In the canine model of acute inflammation, the overall treatment effects as well as the treatment by time interactions were strongly significant (P<0.001) for both drugs. Oral ibuprofen proved uniquely effective at the earliest time point, while all ibuprofen formulations were effective at treating pain at 8.5 and 24.5 hours post-induction. Similarly, all celecoxib formulations (oral and topical) were equally effective at 8.5 and 24.5 hours post-induction.DEL formulations of ibuprofen and celecoxib successfully introduced these NSAIDs into synovial fluid at concentrations similar to those observed in circulation. Furthermore, these formulations reduced symptoms of pain associated with acute inflammation. Oral and transdermally delivered NSAIDs have similar pain relief effects; therefore, a replacement or combinatorial treatment may provide a more stable pain relief profile. In conclusion, this work supports further investigation of TD products in the treatment of regional inflammatory events." @default.
• W2900932809 created "2018-11-29" @default.
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• W2900932809 date "2018-11-01" @default.
• W2900932809 modified "2023-09-27" @default.
• W2900932809 title "Penetration and efficacy of transdermal NSAIDs in a model of acute joint inflammation" @default.
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• W2900932809 doi "https://doi.org/10.2147/jpr.s177967" @default.
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