Pharmacokinetics of ceftriaxone in freshwater crocodiles (Crocodylus siamensis) after intramuscular administration at two dosages.

Abstract

One of the major obstacles to the successful treatment of infectious disease in freshwater crocodile species is incorrect dosing of antibiotics. There are few reports on pharmacokinetics and dosage regimens of antimicrobial drugs in crocodiles. The purpose of the present study was to clarify the pharmacokinetic characteristics of ceftriaxone (CEF) in Siamese freshwater crocodiles (Crocodylus siamensis). Freshwater crocodiles, Crocodylus siamensis, in breeding farms were treated with a single intramuscular administration of CEF at two dosages, 12.5 and 25mg/kg body weight (b.w.). Blood samples were collected at preassigned times up to 168hr. The plasma concentrations of CEF were measured by a validated method through liquid chromatography tandem-mass spectrometry. CEF plasma concentrations were quantified up to 72 and 96hr after low- and high-dose administration, respectively. The Cmax values of CEF were 24.61±5.15µg/ml and 26.39±2.81µg/ml at dosages of 12.5 and 25mg/kg b.w., respectively. The AUClast values increased in a dose-dependent fashion. The half-life values were not statistically different between the groups (around 20hr). The average binding percentage of CEF to plasma protein was 53.78±2.11%. Based on the pharmacokinetic data, susceptibility break-point and the surrogate PK-PD index (T>MIC, 0.2 μg/ml), i.m. administration of CEF at a dose of 12.5mg/kg b.w. might be appropriate for initiating treatment of susceptible bacterial infections in freshwater crocodiles.