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.
Keywords: azithromycin; freshwater crocodiles; liquid chromatography-tandem mass spectrometry; pharmacokinetics.
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