Pharmacokinetics of Enrofloxacin in Emu (Dromaius novaehollandiae) Birds After Intravenous and Oral Bolus Administration

Abstract

Pharmacokinetics of enrofloxacin was studied after intravenous and oral bolus administration at 10 mg/kg in healthy emus aged between 18 and 24 months. Blood samples were collected from jugular vein at predetermined time intervals after drug administration. Enrofloxacin and its active metabolite ciprofloxacin in plasma were determined by HPLC. Plasma concentrations versus time were analyzed by a non-compartmental analysis. For i.v. and oral bolus dose of administration, elimination half-life (t 1/2b ) was 4.364 ± 0.179 and 4.125 ± 0.361 h, respectively; AUC 0-? was 20.085 ± 3.493 and 16.056 ± 1.436 lg h/mL, respectively; mean residence time (MRT) was 5.105 ± 0.216 and 6.616 ± 0.475 h, respectively; volume of distribution was 3.921 ± 1.005 and 3.171 ± 0.296 L/kg, respectively and total body clearance was 0.629 ± 0.164 and 0.507 ± 0.003 L/h kg, respectively. Mean absolute bioavailability for enrofloxacin after oral administration was 79.941 ± 7.147 %. The metabolite ciprofloxacin could be detected from 15 min to 24 h following i.v. and oral administration of enrofloxacin. The ratio of AUC 0-t cipro/AUC 0-t enro was 7.764 and 9.031 %, respectively for i.v. and oral administration of enrofloxacin. The t 1/2b and MRT of the metabolite were longer than those of parent substance. From the PK/PD indices such as C max /MIC, AUC/MIC and C max /MPC, AUC/MPC study, the recommended doses of enrofloxacin in emu birds were 10 mg/kg body weight once daily for i.v. and oral routes against organisms susceptible to 0.25 and 0.125 lg/mL, respectively. Taking the PAE and active metabolite ciprofloxacin into consideration, it is recommended that enrofloxacin could be used at the dose rate of 10 mg/kg at every 24 h even against the organisms susceptible to 0.5 lg/mL. Abbreviations bElimination rate constant AUC 0-t Area under the concentration vs. time curve 0 to time AUC 0-? Area under the concentration-time curve 0 to infinity AUMC 0-t Area under the first moment curve from 0 to time AUMC 0-? Area under the first moment curve from 0 to infinity MRT Mean residence time MAT Mean residence time

Pharmacokinetic and pharmacodynamic integration of enrofloxacin againstSalmonellaEnteritidis after administering to broiler chicken by per-oral and intravenous routes

“…The C max values of enrofloxacin achieved in this study after administering through the PO and IV routes to chickens were greater than the break-point MIC for fluoroquinolone drugs [15]. The bioavailability of enrofloxacin was calculated to be 98.60% ± 8.90% after PO administration in this study; previously, absolute bioavailabilities of enrofloxacin have been reported after oral administration in broiler chicken (77.47% ± 5.86% and 80.10%) [14], emu (79.94% ± 7.15%) [21], and sheep (94.60%) [35]. In this study, the higher bioavailability (98.60% ± 8.90%) of enrofloxacin after oral administration might be due to the extended T 1/2 , which may induce elevated AUC values.…”

“…It is observed in this study that the elimination half-life of enrofloxacin is lengthy, which demonstrates that this drug has the advantage of maintaining an effective concentration in the body; thus, providing an extended time for interaction of the drug with the pathogen. The T 1/2 of enrofloxacin in chicken after administering through IV route (12.8 h) was longer than the value in emu (4.36 h) [21], pigs (4.99 h) [22], calves (3.88 h) [22], dogs (4.07 h) [23], and horses (6.7 h) [24], and shorter than the values observed in pigs (26.6 h) and American alligators (21.05 h) [2225]. In this study, the T 1/2 of enrofloxacin in chicken after administering through the PO route was 25.8 h, which is similar to that in elephant (18.4 h) [26], almost double that in African penguin (13.79 h) [27] and broiler chicken (14.23 h) [28], but much higher than that in emu (4.125 h) [21] and houbara bustard (6.80 h) [29].…”

Pharmacokinetics in Penguins Compared to Other Avian Species: A Review of Enrofloxacin and Voriconazole

“…For the pharmacokinetics of enrofloxacin in birds, chickens have been studied extensively and a comprehensive population analysis by Guo et al report that after IV administration 30% of enrofloxacin was metabolized to ciprofloxacin in chickens . For the Australian emu (Dromaius novaehollandiae), a study that compared both enrofloxacin and ciprofloxacin concentrations following IV and oral administration report that the AUC 0‑t for ciprofloxacin was 7.7% and 9% of enrofloxacin for IV and oral, respectively . For the studies on penguins reported in this review, Wack et al report that for the African penguin, the ciprofloxacin concentrations were below the limit of quantitation (0.05 μg/mL) after both oral and IV administration and so conversion could not be estimated.…”

“…61 For the Australian emu (Dromaius novaehollandiae), a study that compared both enrofloxacin and ciprofloxacin concentrations following IV and oral administration report that the AUC 0-t for ciprofloxacin was 7.7% and 9% of enrofloxacin for IV and oral, respectively. 62 For the studies on penguins reported in this review, Wack et al 33 report that for the African penguin, the ciprofloxacin concentrations were below the limit of quantitation (0.05 μg/mL) after both oral and IV administration and so conversion could not be estimated. The lack of information on the conversion of enrofloxacin to ciprofloxacin for these species is another limitation of the existing pharmacokinetic data for penguins.…”