Comparative in vitro biotransformation of fipronil in domestic poultry using liver microsome.

Domestic poultry are among the non-target species of exposure to fipronil, but limited information is available on the metabolic effects of fipronil exposure in avian. We investigated the comparative capacity of in vitro biotransformation of fipronil among chicken, duck, quail, goose, and rat. Interspecies differences in kinetic parameters were observed; the clearance rate calculations (Vmax/Km) indicated that chicken and duck are more efficient in the cytochrome P450-mediated metabolism of fipronil to sulfone than quail, goose and rat. The lower hepatic clearance of fipronil in quail, goose and rat, suggested that fipronil sulfone may serve as a biomarker to indicate fipronil exposure in these species.

Pharmacokinetic characteristics of azithromycin in freshwater crocodiles (Crocodylus siamensis) after intramuscular administration at three different dosages.

The study evaluated the pharmacokinetic features of azithromycin (AZM) in 15 freshwater crocodiles (Crocodylus siamensis) in Thailand. The crocodiles were administered a single intramuscular (i.m.) injection of AZM at three different dosages of 2.5, 5, and 10 mg/kg body weight (b.w.). Blood samples were collected at pre-assigned times up to 168 h. The plasma concentrations of AZM were measured using a validated liquid chromatography-tandem mass spectrometry method. The plasma concentration of AZM were quantifiable for up to 168 h after i.m. administration at the three different dosages. A non-compartmental model was used to fit the plasma concentration of AZM versus the time curve for each crocodile. The elimination half-life values of AZM were 33.70, 38.11, and 34.80 h following i.m. injection after dosages of 2.5, 5, and 10 mg/kg b.w., respectively. There were no significant differences among groups. The results indicated that the overall rate of elimination of AZM in freshwater crocodiles was relatively slow. The maximum concentration and area under the curve from zero to the last values of AZM increased in a dose-dependent fashion. The average binding percentage of AZM to plasma protein was 48.66%. Based on the pharmacokinetic data, the susceptibility break-point and the surrogate PK-PD index (T > MIC), the intramuscular administration of AZM at a dose of 10 mg/kg b.w. might be appropriate for the treatment of susceptible bacterial infections (MIC < 4 µg/ml) in freshwater crocodiles.

Pharmacokinetic characteristics of danofloxacin in green sea (Chelonia mydas) and hawksbill sea (Eretmochelys imbricata) turtles.

To date, the number of green sea and hawksbill sea turtles is in decline due to environmental, anthropogenic, and pathological factors. The present study described the pharmacokinetic characteristics of danofloxacin (DNX) in green sea and hawksbill sea turtles, following single intravenous (i.v.) and intramuscular (i.m.) administrations at single dosages of 6 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 168 h. DNX in the harvested plasma was cleaned up using liquid-liquid extraction and analyzed using a validated high-performance liquid chromatography method with fluorescence detection. The pharmacokinetic analysis was performed using a non-compartmental approach. DNX was quantifiable from 5 min to 168 h after i.v. and i.m. administrations at an identical dosage in both turtle types. No statistical differences were found in the pharmacokinetic parameters between green sea and hawksbill sea turtles. The long elimination half-life value of DNX obtained in green sea (35 h) and hawksbill sea (30.21 h) turtles was consistent with the quite large volume of distribution and the slow clearance rate. The high values of absolute bioavailability (87%-94%) should be advantageous for clinical use of DNX in sea turtles. According to the pharmacokinetic-pharmacodynamic surrogate (AUC0-24 /MIC > 125), DNX is predicted to have antibacterial success for disease caused by bacteria with MIC < 0.04 µg/ml.