Abstract
Oral squamous cell carcinoma (SSC) has been reported in both managed and wild populations of bottlenose dolphins and similarly, is a common neoplasia in humans and domestic species.1,2,3 Treatment with intent to cure these lesions is best achieved with surgical excision in any species.1,4 However, if these lesions are not surgically accessible, are incompletely excised or if the risks of anesthesia and surgery in an individual outweigh the benefit of excision, alternative options for therapy are needed. Piroxicam is an enolic benzothiazine and a potent nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class which nonselectively suppresses the production of the proinflammatory enzymes, cyclooxygenase-1 and -2 (COX-1 and 2).5 COX-1 production supports tumor growth by playing a role in prostaglandin and vascular epidermal growth factor production.5 COX- 2 production is the main ultraviolet (UV)-responsive isoform in human skin and it is known to be involved with UV-induced inflammation and apoptosis of skin cells and subsequent formation of actinic keratoses (principle precursor of SCC) and squamous cell carcinoma.4 In addition to its nonspecific COX enzyme inhibition, piroxicam downregulates the production of prostaglandin and thromboxanes and inhibits ornithine decarboxylase induction, both processes known to participate in carcinogenesis.6 Piroxicam has been successful in chemoprevention and reduction in tumor size of nonmelanoma skin cancers and precursors.2,3,5 Based on these data and drug properties, piroxicam has been prescribed in managed bottlenose dolphins that have known oral SCC or precursor lesions and there has been anecdotal clinical success in the authors experience. Use of NSAIDs in cetaceans is a common practice but adverse effects of piroxicam and other NSAIDs have been seen in the authors experience and have been reported in both unpublished and published data.2,7 With the promise of the therapeutic value of piroxicam in the treatment of oral SCC in dolphins and in light of the potential for adverse effects, investigation of this drugs pharmacokinetic action within this species is warranted. The purpose of this study is to document the pharmacokinetic action of single dose piroxicam in bottlenose dolphins and to evaluate the efficacy of current dosing recommendations used by the authors. It is hypothesized that the pharmacokinetic action of piroxicam will be similar to that of meloxicam in bottlenose dolphins that has been previously reported.8 Twenty-eight dolphins housed at SeaWorld California and SeaWorld Florida were included in this study. All dolphins were given one single oral dose of piroxicam at 0.1 milligrams per kilogram (mg/kg) (rounded to the nearest 5 mg). Blood samples were collected for plasma piroxicam concentration at time points T=1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 168, 240 h. Animals were pooled so that there were at minimum n=4 animals for each time point. Samples were sent to and are pending at the Clinical Pharmacology Laboratory in the College of Veterinary Medicine of North Carolina State University for high-pressure liquid chromatography (HPLC) analysis for plasma drug concentration.
Acknowledgements
The authors would like to thank the United States Navy Marine Mammal Program for allowing Navy animals currently housed at SeaWorld San Diego to participate in this study. Authors would also like to thank the veterinary technical and training support staff of SeaWorld San Diego and Orlando for assistance with sampling for this study.
* Presenting author
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