Penetration and efficacy of transdermal NSAIDs in a model of acute joint inflammation
| Autor: | Joseph Gabriele, Stephanie Kelly, David Charles Baranowski, Beth Buchanan, Heather C Dwyer, Joseph A Araujo |
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| Rok vydání: | 2018 |
| Předmět: |
Osteoarthritis
canine model 03 medical and health sciences 0302 clinical medicine Oral administration medicine Synovial fluid pain 030212 general & internal medicine Journal of Pain Research Adverse effect Original Research ibuprofen Transdermal 030203 arthritis & rheumatology celecoxib business.industry Therapeutic effect medicine.disease Ibuprofen osteoarthritis Anesthesiology and Pain Medicine Anesthesia Celecoxib business medicine.drug |
| Zdroj: | Journal of Pain Research |
| ISSN: | 1178-7090 |
| Popis: | David Charles Baranowski,1 Beth Buchanan,1 Heather C Dwyer,1 Joseph P Gabriele,1 Stephanie Kelly,2 Joseph A Araujo3 1Department of Research and Development, Delivra Corp., Charlottetown, PE, Canada; 2Vivocore Inc, Toronto, ON, Canada; 3InterVivo Solutions Inc, Toronto, ON, Canada Purpose: 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.Methods: 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.Results: After seven days of chronic topical administration, DelivraTM (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 |
| Databáze: | OpenAIRE |
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