Comparative Evaluation of the Renal Effects of a Seven-Day Therapy with Flunixin Meglumine, Ketoprofen and Meloxicam in Budgerigar (Melopsittacus)
American Association of Zoo Veterinarians Conference 2004

Marcia Elisa Pereira, MedVet, MS; Karin Werther, MedVet, Dr. Med.Vet.

Departamento de Patologia Veterinaria, Faculdade de Ciencias Agrarias e Veterinaria, Universidade Estadual Paulista-UNESP, Jaboticabal, São Paulo, Brazil

Abstract Introduction

Nonsteroidal anti-inflammatory drugs (NSAID) are widely used for the treatment of inflammatory diseases and pain relief in bird clinical practice. The NSAIDs promote analgesic effects, but also present adverse effects. However, little is known about their effect in birds. Low doses of flunixin meglumine caused glomerular injuries after a 7-day treatment in northern bobwhite (Colinus virginianus).3 Renal injuries, renal and visceral gout and death were described in Siberian crane followed treatment with flunixin meglumine.1 But renal injury was not observed in quails (Coturnix coturnix japonica) treated with flunixin meglumine at 3.4 mg/kg and in quails treated with meloxicam at 1.0 mg/kg for 3 days or 5 days.4 Currently meloxicam and ketoprofen are often used in avian clinical practice, since it is believed to produce less clinically important adverse effects than flunixin meglumine.

Material and Methods

Thirty-two healthy budgerigars (young male and females) were used in this study. Food and water were available ad libitum. Birds were randomly assigned to 1 of 4 treatments: group 1 - distilled water alone; group 2 - flunixin meglumine (Banamine®) at 5.5 mg/kg; group 3 - ketoprofen (Ketofen®) at 2.5 mg/kg and group 4 - meloxicam (Bioflac®) at 0.1 mg/kg. All drugs were dissolved in distilled water at such concentrations that the dose was delivered in a volume of 0.04 ml for all experimental groups. All birds were injected at chest muscle alternately each 24 hr for 7 days. Following treatment period, blood samples were collected to perform plasma uric acid dosage, and each bird was immediately euthanatized. Kidneys were assessed by macroscopic examination, following histologic processing, staining with hematoxylin-eosin and microscopic examination.

Results and Discussion

Plasma uric acid values did not present significant differences among groups. Other authors reported no significant differences on plasma uric acid values in northern bobwhite quails, although renal injuries were present.3 Therefore, a normal uric acid value does not mean healthy kidneys.2 Increasing plasma uric acid level in birds only occurs during extensive tubular disease or due to severe dehydratation.6 No bird on control group presented either glomerular or tubular injuries. Birds treated with ketoprofen presented with glomerular vacuoles (12.5%) and tubular dilatation (12.5%).

Macroscopically examination revealed one bird (1/8) presenting renal paleness after treatment with meloxicam. Furthermore, 12.5% of birds presented glomerular vacuoles, 12.5% glomerular congestion and 12.5% glomerular congestion after treatment with meloxicam. Even selective COX-2 inhibitor NSAIDs such as meloxicam produced adverse effects over kidneys, whereas the advantage of using specific COX-2 inhibiting NSAIDs is related to only gastrointestinal tract.5

Birds treated with flunixin meglumine presented mesangial hypocellularity (25%) and tubular necrosis (75%). Some authors found similar results in northern bobwhite quails treated with flunixin meglumine such as glomerular injuries, amorphous mineralized deposition, granular and basophilic on renal glomeruli in all birds treated,3 whereas more aggravated injuries than our results were found in this study. A possible explanation should consider the sensibility of this bird species as well as absence of hydric fasting in this study. Since other authors did not observe renal injury in healthy quails treated with flunixin meglumine at 3.12 to 3.43 mg/kg support this idea.4 Tubular necrosis was significant in birds treated with flunixin meglumine, which demonstrates that this NSAID has more potential to cause tubular damage in budgerigars when compared to ketoprofen and meloxicam, therefore it should not be used. Further studies are necessary to evaluate the effects of treatments using ketoprofen and meloxicam at long lasting administration periods.

Conclusion

Ketoprofen, meloxicam and flunixin meglumine present great potential to cause renal injuries in clinically healthy budgerigars submitted to 7-days treatment, whereas the flunixin meglumine presents higher potential to cause tubular and glomerular injuries, followed by meloxicam and ketoprofen.

Literature Cited

1.  Clyde VL, Paul-Murphy J. 1999. Avian analgesia. In: Fowler ME, Miller RE. Zoo and Wild Animal Medicine Current Therapy. 4. W.B. Saunders, Philadelphia, Pennsylvania. Pp. 309–314.

2.  Hochleithnner M. 1994. Biochemistries. In: Ritchie BW, Harrison GJ, Harrison LR. Avian Medicine: Principles and Application. Wingers, Lake Worth, Florida. Pp. 223–245.

3.  Klein PN, Charmatz K, Langenberg J. 1994. The effect of flunixin meglumine (Banamine) on the renal function in northern bobwhite (Colinus virginianus): an avian model. In: Annual Conference of American Association of Zoo Veterinarians Proceedings. Pittsburgh, Pennsylvania. Pp. 128–131.

4.  Lucas SS. 2003. Avaliacao Laboratorial e Histopatologica de Codornas (Coturnix coturnix japonica) Submetidas a Terapia Anti-inflamatoria Nao Esteroide por Extrapolacao Alometrica [Doctor in Veterinary Medicine Thesis]. Universidade Federal de Santa Maria, Santa Maria, Brazil.

5.  Stichtenoth DO, Frölich J. 2003. The second generation of COX-2 Inhibitors—what advantages do the newest offer. Drugs. 63: 33–45.

6.  Styles DK, Phalen DN. 1998. Clinical avian urology. Seminars in Avian and Exotic Pet Medicine. 7: 104–113.

 

Speaker Information
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Marcia Elisa Pereira, MedVet, MS
Departamento de Patologia Veterinaria
Estadual Paulista-UNESP
Jaboticabal, SP, Brazil


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