The Use of Azithromycin in Zoological Medicine, with Emphasis on Its Pharmacokinetics in the Blue and Gold Macaw (Ara ararauna)
Azithromycin belongs to a subclass of macrolide antibiotics classified as azalides. Its mechanism of action is similar to that of the structurally related erythromycin: it interferes with bacterial protein synthesis by binding to the 50S ribosomal subunit.6,8 It has a broad spectrum of activity in vitro against a number of potential pathogens, including gram-positive and gram-negative organisms, spirochaetes, anaerobes, and Chlamydia trachomatis. Azithromycin has been determined to have in vitro activity against enteric bacterial pathogens including Campylobacter spp. and enteropathogenic/enterotoxigenic Escherichia coli, Shigella spp., and Salmonella spp.7 Despite macrolides generally being considered bacteriostatic, azithromycin has demonstrated in vitro cidal activity against a variety of intracellular pathogens and has been used for treatment of toxoplasmosis, borreliosis, malaria, cryptosporidiosis, chlamydiosis, and mycobacteriosis (Mycobacterium avium complex) in humans.6
Azithromycin has greater tissue penetration and has been shown to have a longer elimination half-life than erythromycin.4,7 Animal and human studies have shown that orally administered azithromycin is rapidly absorbed and distributed extensively into tissues, with peak tissue concentrations exceeding those in the serum, and persisting for longer periods.5,7,9 Also, concentrations of azithromycin in the liver, lung, kidney, ileum, and brain were higher than serum concentrations in rats and rabbits following oral administration when compared to erythromycin.3 It should also be noted that there were no toxic effects noted in rats, rabbits, and dogs when azithromycin was administered for several months in amounts exceeding the therapeutic dose.3 Although the number of published reports of azithromycin in zoological medicine (i.e., laboratory animals; reptiles,1 birds,6 and other exotic pets; wildlife; and zoo animals2) are limited, its therapeutic potential in these animals needs to be pursued.
Because we have limited data on azithromycin in zoological medicine, a study was designed to determine the pharmacokinetics of azithromycin in blue and gold macaws (Ara ararauna), a species commonly seen both in clinical practice and in displays in zoos and wildlife parks. This project included both oral and intravenous administration of azithromycin to determine bioavailability and absorption. Azithromycin (10 mg/kg) was administered orally via crop gavage to five birds and intravenously to five birds, and blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 h post-azithromycin administration. Following a 4-week washout period, the study was repeated, with the first five birds receiving the intravenous dose and the second five birds receiving the oral dose.
Samples were analyzed using a validated liquid chromatography/mass spectrometer, and pharmacokinetic parameters were determined using non-compartmental analysis. Parameters calculated following dosing were area under the plasma concentration versus time curve (AUC), area under the first moment curve (AUMC), mean residence time (MRT), volume of distribution (Vd), plasma clearance (Clp), elimination rate constant (kel), apparent terminal half-life (t½), and bioavailability (F).
Based on the plasma data generated in this study, we recommend azithromycin at a dose of 10–20 mg/kg PO q 48 h × 5 treatments for non-intracellular infections and 40 mg/kg PO q 24 h × 30 days for intracellular infections (i.e., Chlamydophila sp.). The results of this study may have clinical applications for other related avian species and should stimulate studies on the pharmacokinetics of azithromycin in other nontraditional, zoo, or wild animals.
This work was supported in part by a grant from the Faculty Development Awards and the University Small Research Grants, Kansas State University. The assistance in various aspects of this research by Heather Henry, CVT; Arnold Stillman; Clif Martel; and Ian Hutchison of Busch Gardens Tampa Bay are also gratefully acknowledged.
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