Abstract
To the best of the authors’ knowledge, there are a few reports on pharmacokinetics in animals. No information exists on the pharmacokinetics of clarithromycin (CLA) in freshwater crocodiles including Crocodylus siamensis, but PK parameters have been evaluated in tortoise, beagles, rats and foals.1-3 The lack of information regarding effective dosing regimens makes designing treatment plans difficult and, in their absence, substantial direct and indirect mortality in freshwater crocodiles can result.4
Clarithromycin is a new β-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 (IV) or intramuscular (IM) administration at a dosage of 2.5 mg/kg body weight (BW). Blood samples were collected at assigned times up to 168 h. CLA plasma samples were cleaned up using liquid-liquid extraction and analyzed by a validated liquid chromatography tandem-mass spectrometry (LC-MS/MS). CLA was quantifiable from 5 minutes to 72 hours after IV administration, whereas it was detectable for 168 hours after IM 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 t½λz value, similar for both routes (20 hours), indicated that the overall rate of elimination of CLA in crocodiles is relatively slow. The average IM 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.5 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.
Acknowledgements
This work was funded by the Thailand Research Fund, Bangkok, Thailand (research grant number: RSA6180033) and the Kasetsart University Research and Development Institute (KURDI), Bangkok, Thailand. The authors thank ThothPro for supplying the ThothPro software (4.3.0v).
*Presenting author
+Student presenter
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