Pharmacokinetics of an orally administered methylcellulose formulation of gallium maltolate in neonatal foals |
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| Authors: | M. K. CHAFFIN V. FAJT R. J. MARTENS C. E. ARNOLD N. D. COHEN M. O’CONOR R. J. TAYLOR L. R. BERNSTEIN |
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| Affiliation: | 1. Department of Large Animal Clinical Sciences, Equine Infectious Disease Laboratory, Texas A&M University, College Station, TX;2. Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX;3. Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX;4. Terrametrix, Menlo Park, CA, USA |
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| Abstract: | Chaffin, M. K., Fajt, V., Martens, R. J., Arnold, C. E., Cohen, N. D., O’Conor, M., Taylor, R. J., Bernstein, L. R. Pharmacokinetics of an orally administered methylcellulose formulation of gallium maltolate in neonatal foals. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365‐2885.2009.01150.x. Gallium is a trivalent semi‐metal with anti‐microbial effects because of its incorporation into crucial iron‐dependent reproductive enzyme systems. Gallium maltolate (GaM) provides significant gallium bioavailability to people and mice following oral administration and to neonatal foals following intragastric administration. To study the prophylactic and therapeutic effects of GaM against Rhodococcus equi pneumonia in foals, we developed a methylcellulose formulation of GaM (GaM‐MCF) for oral administration to neonatal foals. Normal neonatal foals were studied. Six foals received 20 mg/kg and another six foals received 40 mg/kg of GaM‐MCF orally. Serial serum samples were collected and serum gallium concentrations were determined using inductively coupled plasma mass spectroscopy. Gallium was rapidly absorbed (Tmax of 4 h), and a mean Cmax of 0.90 or 1.8 μg/mL was achieved in foals receiving 20 or 40 mg/kg respectively. Marked variability existed in Cmax among foals: only half of the foals receiving 20 mg/kg attained serum concentrations of >0.7 μg/mL, a level suggested to be therapeutic against R. equi by previous studies. Mean elimination half‐life was 32.8 or 32.4 h for foals receiving 20 or 40 mg/kg respectively. The results of this study suggest that at least 30 mg/kg orally every 24 h should be considered in future pharmacodynamic and efficacy studies. |
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