Pharmacokinetics of carprofen in Siamese crocodiles (Crocodylus siamensis)

Abstract

Carprofen (CAR) is an NSAID commonly used in veterinary medicine that preferentially inhibits cyclooxygenase-2 (COX-2), thereby mitigating inflammation and pain while minimizing adverse effects linked to cyclooxygenase-1 (COX-1) inhibition. This study characterizes the pharmacokinetics of CAR in Siamese crocodiles (Crocodylus siamensis) and was conducted at an ambient temperature range of 27–30 °C following single intravenous (IV) or intramuscular (IM) administration at 2 mg/kg, and IM administration at 4 mg/kg. Plasma concentrations were determined using a validated high-performance liquid chromatography method with ultraviolet detection (HPLC-UV). Pharmacokinetic parameters were derived using non-compartmental analysis (NCA). After IM administration, CAR exhibited dose-dependent increases in peak plasma concentrations (C_max: 4.15 μg/mL at 2 mg/kg; 6.64 μg/mL at 4 mg/kg). The elimination half-life (t_1/2λz) was prolonged following IM injection (37.00–40.22 h) compared to IV administration (25.69 h), suggesting flip-flop kinetics. The volume of distribution (Vd) ranged from 0.43 to 0.68 L/kg. The IM bioavailability (F) was calculated as 123.75 % at 2 mg/kg and 94.96 % at 4 mg/kg, potentially reflecting overestimation due to between-group variability in clearance, absence of a cross-over design, or factors such as analytical variation, vehicle effects, or lymphatic absorption. Plasma protein binding ranged from 73 % to 82 %. These findings indicate sustained systemic exposure and high bioavailability of CAR in C. siamensis, supporting its potential as a long-acting analgesic. Future studies should assess pharmacodynamic responses and therapeutic efficacy in clinical settings to optimize dosing regimens.