pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs药物动力学的注射强力霉素hyclate长效配方的狗.pdfVIP

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pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs药物动力学的注射强力霉素hyclate长效配方的狗.pdf

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pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs药物动力学的注射强力霉素hyclate长效配方的狗

Gutiérrez et al. Acta Veterinaria Scandinavica 2012, 54:35 /content/54/1/35 RESEARCH Open Access Pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs 1 1 2 1 3* Lilia Gutiérrez , Zazil-Ha Velasco , Carlos Vázquez , Dinorah Vargas and Héctor Sumano Abstract Based on its PK/PD ratios, doxycycline hyclate (DOX-h), a time-dependant antibacterial, is ideally expected to achieve both sustained plasma drug concentrations at or slightly above the MIC level for as long as possible between dosing intervals. Pursuing this end, a poloxamer-based matrix was used to produce a long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its SC injection to dogs (≤ 0.3 mL per injection site), and results compared with the oral (PO) and IV pharmacokinetics of DOX-h, prepared as tablet or as freshly made solution. A crossover (4 x 4 x 4) study design was employed with 12 Mongrel dogs, with washout periods of 21 days, and at dose of 10 mg/kg in all cases. DOX-h-LA showed the greatest values for bioavailability (199.48%); maximum serum concentration (Cmax) value was 2.8 ± 0.3 with a time to reach Cmax (Tmax) of 2.11 ± 0.12 h and an elimination half-life of 133.61 ± 6.32 h. Considering minimum effective serum concentration of 0.5 μg/mL, a dose-interval of at least 1 week h can be achieved for DOX-h-LA, and only 48 h and 24 h after the IV or PO administration of DOX-h as a solution or as tablets, respectively. A non-painful small bulge, apparently non-inflammatory could be distinguished at injection sites. These lumps dissipated completely in 30 days in all cases. Keywords: Doxycycline, Dog, Pharmacokinetics, Long-acting,