Pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs

Acta Vet Scand. 2012 Jun 8;54(1):35. doi: 10.1186/1751-0147-54-35.

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.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics*
  • Area Under Curve
  • Biological Availability
  • Cross-Over Studies
  • Dogs / metabolism*
  • Doxycycline / administration & dosage
  • Doxycycline / blood
  • Doxycycline / pharmacokinetics*
  • Female
  • Half-Life
  • Injections, Intravenous / veterinary
  • Injections, Subcutaneous / veterinary
  • Male
  • Poloxamer / administration & dosage
  • Poloxamer / pharmacokinetics
  • Tablets / pharmacokinetics

Substances

  • Anti-Bacterial Agents
  • Tablets
  • Poloxamer
  • Doxycycline