Pharmacokinetic Characteristics of Tolfenamic Acid in Freshwater Crocodiles (Crocodylus siamensis)

The present study was undertaken to characterize the plasma kinetic disposition of tolfenamic acid (TA) in freshwater crocodiles. In total, 15 freshwater crocodiles were used in the experiment and randomly divided into three groups, with TA administered at 2 mg/kg body weight (b.w.) intravenously (IV) or at 2 or 4 mg/kg b.w. intramuscularly (IM). Blood samples were collected at predetermined times up to 168 h after IV or IM drug administration. Plasma concentrations of TA were determined using validated high-performance liquid chromatography with a UV detector and then analyzed based on the non-compartmental method. The maximum concentration values of TA were 3.03 µg/mL and 6.83 µg/mL following IM administration at a dose of 2 mg/kg b.w. or 4 mg/kg b.w., respectively. The elimination half-lives were 21.89 h (2 mg/kg; IV), 17.74 h (2 mg/kg; IM), and 13.57 h (4 mg/kg; IM). Following IV administration, the volume of distribution and clearance were 1.58 L/kg and 50.04 mL/h/kg, respectively. The absolute IM bioavailability was 71.0% at a dose of 2 mg/kg b.w. and 92.63% at a dose of 4 mg/kg b.w. The average ± SD of plasma protein binding of TA was 26.15 ± 4.93%. Good bioavailability levels and favorable plasma concentrations of TA were obtained in freshwater crocodiles after IM administrations, considering that this is the preferred route of drug administration in freshwater crocodiles. Multi-dose and pharmacodynamic studies are needed to better establish the safety and efficacy of using TA in this crocodilian species.