Pharmacokinetics and pharmacodynamics of danofloxacin in serum and tissue fluids of goats following intravenous and intramuscular administration

Abstract

Objective: To determine the pharmacokinetics and pharmacodynamics of danofloxacin in goats and the concentrations required to induce bacteriostasis, bactericidal activity, and bacterial elimination.

Animals: 6 healthy British Saanen goats.

Procedure: Danofloxacin (1.25 mg/kg of body weight) was administered i.v. and i.m. in a cross-over design with 14 days between treatments. A tissue cage was used for evaluation of drug distribution into transudate and exudate. The ex vivo antibacterial activity of danofloxacin in serum, exudate, and transudate against a caprine isolate of Mannheimia haemolytica was determined. Pharmacokinetic and pharmacodynamic data were integrated to determine the ratio of the area under the concentration versus time curve to the minimum inhibitory concentration of danofloxacin (AUIC).

Results: Elimination half-lives of danofloxacin in serum were 4.67 and 4.41 hours after i.v. and i.m. administration, respectively. Volume of distribution was high after administration via either route, and bioavailability was 100% after i.m. administration. Rate of penetration into exudate and transudate was slow, but elimination half-lives from both fluids were approximately twice that from serum. Drug concentrations in serum, exudate, and transudate for 9 to 12 hours after administration induced marked ex vivo antibacterial activity. For serum, AUIC24h values required for bacteriostasis, bactericidal effect, and bacterial elimination were 22.6, 29.6, and 52.4, respectively. Similar values were obtained for exudate and transudate.

Conclusions and clinical relevance: Integration of danofloxacin pharmacokinetic and pharmacodynamic data obtained in goats may provide a new approach on which to base recommendations for therapeutic dosages.