Comparative pharmacokinetics of ceftazidime in Siamese crocodiles after intramuscular administration between forelimb and hindlimb

The pharmacokinetics of ceftazidime (CAZ) were evaluated in Siamese crocodiles (Crocodylus siamensis) following a single 20 mg/kg intramuscular administration into either the forelimb or hindlimb. The pharmacokinetic profiles were substantially equivalent between the injection sites, with no significant differences (p > 0.05) in key parameters (Cmax, Tmax, AUC, t1/2λz, Cl, and bioavailability). CAZ was absorbed rapidly at both injection sites, with a median Tmax value of 0.5 h and high bioavailability (90.35% for the forelimb, 86.12% for the hindlimb), indicating efficient systemic exposure, regardless of the injection site. The peak plasma concentrations exceeded the reported MIC of many clinically significant Gram-negative pathogens The observed Cmax and an estimated T > MIC of approximately 50 h suggested that the dosing regimen may have achieved pharmacodynamically effective concentrations against susceptible pathogens, including Pseudomonas aeruginosa, in crocodilians. The prolonged t1/2λz value and the low Cl rate observed (up to 49.02 h and 4.42 mL/hr/kg, respectively) suggested infrequent dosing may be feasible. Despite theoretical concerns about the renal portal system influencing drug distribution in reptiles, no evidence was observed of any altered pharmacokinetics between limbs. Comparative analysis with other ectotherms revealed species-specific variation, highlighting the need for targeted dosing strategies. Further studies are warranted, involving repeated dosing and pharmacodynamic evaluation, to optimize CAZ use in crocodilian medicine.