Pharmacokinetics of ketoprofen have been established in numerous mammalian species; however, no published pharmacokinetic data exist for avian species, although some studies have evaluated the pharmacodynamics (Machin et al., 2001) and analgesic effects (Machin & Livingston, 2002) of this nonsteroidal anti-inflammatory drug in ducks. Ketoprofen is a chiral compound that exists as two enantiomers, R()) and S(+) ketoprofen. Products approved for clinical use in both human and veterinary medicine are the racemic mixtures (50:50) of the two enantiomers. Dosage regimens for birds are extrapolated from those of small mammals, although there are anatomic and metabolic differences between avian species and mammals that make extrapolation of drug dosages dangerous (Dorrestein, 1992). In addition, even if dosages for birds were available, extrapolation within the Aves class could potentially be problematic since a previous study comparing pharmacokinetic parameters for nonsteroidal anti-inflammatory drugs reported avian species differences (Baert & DeBacker, 2003). Another concern regarding the use of nonsteroidal anti-inflammatory drugs is that toxic effects may be seen at therapeutic concentrations (MacAllister et al., 1993). This has been demonstrated clinically in male Eider ducks where ketoprofen has been reported to be lethal (Mulcahy et al., 2003). For all of the aforementioned reasons, pharmacokinetic studies are important to determine appropriate therapeutic dosages for avian species. The objective of this study was to establish the pharmacokinetics of intravenous, intramuscular, and orally administered ketoprofen in adult Japanese quail, a popular laboratory animal avian species. A three-period cross-over design was used so that each adult domestic Japanese quail (Coturnix japonica; n 1⁄4 45) received ketoprofen (2 mg/kg) intravenously, intramuscularly, or orally. The average body weight of the birds was 146 g (±26). Twoweek intervals were allowed between each period of the study. No remarkable findings were found on physical examination. Food and water were provided ad libitum throughout the study. The University of California, Davis, Animal Care and Use Committee approved this study. In period 1, quails 1–15 were administered ketoprofen (Ketofen, Fort Dodge, Iowa 50501, USA; 2 mg/kg) intravenously via the right jugular vein; quails 16–30 received ketoprofen (2 mg/kg) intramuscularly in the pectoral muscle; and quails 31–45 received ketoprofen (2 mg/kg) orally via ingluvial gavage. To ensure accurate dosing, the commercial ketoprofen solution was diluted with sterile 0.9% NaCl and administered immediately after dilution. In periods 2 and 3, treatments were altered so that each route of drug administration was delivered in sequence. Blood samples (0.5 mL/sample) were collected from the right jugular vein 1 week prior to drug administration (time 1⁄4 0) and at times 0.08, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, and 8 h following drug administration. Following ketoprofen administration, a maximum of two 0.5 mL blood samples per bird were drawn so that the total volume of blood drawn from each bird did not exceed 1% of the body weight. Blood samples were collected into microtainer tubes containing heparin and centrifuged at 2000 g for 10 min. The plasma was decanted, labeled, and frozen at )20 C until the assays were performed. Ketoprofen concentrations in test plasma for the pharmacokinetic portion were measured using liquid chromatography – mass spectrometry (LC-MS) analysis of protein-precipitated plasma samples (Skinner et al., 2004). Plasma calibrators were prepared by diluting working ketoprofen solutions with drug-free quail plasma to concentrations of 0.01, 0.05, 0.1, 0.25, 0.5, 0.75, 1.0, 2.0, 4.0, 8.0, 16.0, and 32 lg/mL. Quality control (QC) samples (plasma fortified with analytes at concentrations mid-point of the standard curve) were also included. Each sample’s concentration of ketoprofen was determined by the J. vet. Pharmacol. Therap. 28, 399–402, 2005. SHORT COMMUNICATION
Read full abstract
Jun 4, 2009
Thomas Roberts + 1
Open Access