Identification and comparison of marbofloxacin metabolites from the plasma of ball pythons (Python regius) and blue and gold macaws (Ara ararauna) R. P. HUNTER* D. E. KOCH* R. L. COKE   J. W. CARPENTER à & R. ISAZA § *Department of Anatomy & Physiology, Zoological Pharmacology Laboratory, Kansas State University, Manhattan, KS, USA;   San Antonio Zoo, San Antonio, TX, USA; à Department of Clinical Sciences, Kansas State University, Manhattan, KS, USA; § Department of Small Animal Clinical Sciences, University of Florida, Gainesville, FL, USA Hunter, R. P., Koch, D. E., Coke, R. L., Carpenter, J. W., Isaza, R. Identification and comparison of marbofloxacin metabolites from the plasma of ball pythons (Python regius) and blue and gold macaws (Ara ararauna). J. vet. Pharmacol. Therap. 30, 257–262. Marbofloxacin is a veterinary only, synthetic, broad spectrum fluoroquinolone antimicrobial agent. In mammals, approximately 40% of the oral dose of marbofloxacin is excreted unchanged in the urine; the remaining is excreted via the bile as unchanged drug in the feces. The V d ranges from 1.1 (cattle) to 1.3 (dog, goat, swine) L/kg. Because of extra-label use of marbofloxacin in birds and reptiles, this study was designed to determine the profile of metabolites in plasma and compare the circulating metabolite profile between a reptile and an avian species. Six adult ball pythons (Python regius) and 10 blue and gold macaws (Ara ararauna) were used in this study. The macaws were dosed both i.v. and p.o. with a single 2.5 mg/kg administration where as the pythons received a single 10 mg/kg dose both i.v. and p.o. The metabolite profiles of marbofloxacin in the plasma of these species were determined using a high performance liquid chromatography system with a mass spectrometer for detection (LC/MS/MS). Mass spectra data generated from the snake and bird plasma samples were compared with previously reported LC/MS/MS mass spectral data. Evidence does not suggest differences due to route of adminis- tration (i.v. vs. p.o.) in either species. Four chromatographic peaks with resulting daughter spectrum were identified and represent 12 possible metabolite structures. All of the proposed metabolites, except for the N-oxide, appear to be unique to macaws. The potential metabolites identified in macaws appear to be very different than those reported for chickens. (Paper received 15 December 2006; accepted for publication 16 February 2007) Rob Hunter, Elanco Animal Health, 2001 West Main Street, Greenfield, IN 46140, USA. E-mail: hunter_robert_p@lilly.com Supported by the Department of Anatomy & Physiology’s Clinical Research Grant Program, College of Veterinary Medicine Faculty Development Awards, the Univer- sity Small Research Grants, Kansas State University and Busch Gardens Tampa Bay. INTRODUCTION Marbofloxacin has been used in Europe for several years in the pet and livestock species. Marbofloxacin was developed exclu- sively for use in veterinary medicine, and is approved in the USA for the treatment of skin and soft tissue infections in dogs and cats and urinary tract infections (i.e. cystitis) in dogs. This fluoroquinolone is a synthetic, broad spectrum antibacterial agent. The mechanism of action for marbofloxacin is similar to the other fluoroquinolones by impairing the bacterial DNA gyrase which results in rapid bactericidal activity (Boothe, 2001). In mammals, approximately 40% of the oral dose of marbofloxacin is excreted unchanged in the urine; the remaining is excreted via the bile as unchanged drug in the feces, but this has not been confirmed in reptile or avian species (Schneider et al., 1996). We have previously published data on the single-dose plasma pharmacokinetics of marbofloxacin in ball pythons (Python regius) and blue and gold macaws (Ara ararauna; Carpenter et al., 2006; Coke et al., 2006). Because of current extra-label use of J. vet. Pharmacol. Therap. 30, 257–262, doi: 10.1111/j.1365-2885.2007.00845.x. Ó 2007 The Authors. Journal compilation Ó 2007 Blackwell Publishing Ltd 257