Pharmacokinetic profiles of clarithromycin in freshwater crocodiles (Crocodylus siamensis)

Clarithromycin (CLA) is a new beta-lactamase-resistant macrolide antibiotic with potent activity against gram-positive and some gram-negative bacteria. To the authors' best knowledge, limited pharmacokinetic information to establish suitable therapeutic plans is available for freshwater crocodiles. To assess the prudent use of antibiotic in reptiles, this study was conducted to explore the pharmacokinetic characteristics of CLA in the freshwater crocodile, Crocodylus siamensis, following either single intravenous (i.v.) or intramuscular (i.m.) administration at a dosage of 2.5 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 168 h. CLA plasma samples were cleaned up using liquid-liquid extraction, and analysed by a validated liquid chromatography tandem-mass spectrometry (LC-MS/MS). CLA was quantifiable from 5 min to 72 h after i.v. administration, whereas it was detectable for 168 after i.m. administration at an identical dose rate. A non-compartmental model was used to fit the plasma concentration of CLA versus time curve for each crocodile. The t(1/2 lambda z) value, similar for both routes (20 h), indicated that the overall rate of elimination of CLA in crocodiles is relatively slow. The average i.m. F% was complete. The protein plasma bound was found to be about 30%. CLA is a time-dependent antibiotic, and the T > MIC is the best PK/PD predictor for its efficacy. The CLA dosage of 2.5 mg/kg appeared to produce an appropriate value of the PK-PD surrogate that predicts antibacterial success for disease caused by susceptible bacteria.