Oxytetracycline Pharmacokinetics in Rainbow Trout during and after an Orally Administered Medicated Feed Regimen |
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| Authors: | Ron A. Miller Francis R. Pelsor Andrew S. Kane Renate Reimschuessel |
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| Affiliation: | 1. U.S. Food and Drug Administration, Center for Veterinary Medicine, Office of New Animal Drug Evaluation , 7500 Standish Place, Rockville , Maryland , 20855 , USA;2. Department of Environmental and Global Health , College of Public Health and Health Professions, University of Florida , 1225 Center Drive, Gainesville , Florida , 32611 , USA;3. Aquatic Pathobiology Laboratories, Emerging Pathogens Institute, University of Florida , Post Office Box 100009, 2055 Mowry Road, Gainesville , Florida , 32611 , USA;4. U.S. Food and Drug Administration, Center for Veterinary Medicine, Office of Research , 8401 Muirkirk Road, Laurel , Maryland , 20708 , USA |
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| Abstract: | Abstract The pharmacokinetic–pharmacodynamic predictor of antimicrobial activity for tetracyclines is reported to be the area under the concentration–time curve at steady state (AUCss) divided by the minimal inhibitory concentration of the targeted pathogen. Here, we estimate AUCss values for oxytetracycline (OTC) in serum of rainbow trout Oncorhynchus mykiss by using a destructive sampling study design. Seventy-two rainbow trout were fed OTC-medicated feed at 74.7 ± 1.5 mg/kg (mean ± SD) body weight (BW) by oral gavage for 10 consecutive days. Serum was collected from nine fish at 1, 3, 6, 8, 10, 12, 15, and 22 d after dosing began. Serum OTC concentrations were measured by high-performance liquid chromatography with a 0.01-μg/mL limit of detection. The average OTC AUCss was 29.2 μg × h/mL and was estimated using nonlinear mixed-effects modeling and bootstrap resampling techniques. The elimination half-life was estimated as 85.0 h, and the fraction of steady state achieved was estimated as 0.85. The calculated AUCss (24.8 μg × h/mL) following 10 d of oral dosing with 75 mg OTC/kg BW was less than the estimated AUCss. Results suggest that the pharmacokinetics of OTC exposure, including the AUCss, is better evaluated by using multiday dosimetry than by using a standard single-dose protocol. Received September 29, 2011; accepted January 30, 2012 |
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