Ergot alkaloids (EAs) are mycotoxins mainly produced by the fungus Claviceps purpurea. EAs are known to affect the nervous system and to be vasoconstrictors in humans and animals. This work presents recent advances in swine and dairy feeds regarding 11 major EAs, namely ergometrine, ergosine, ergotamine, ergocornine, ergocryptine, ergocristine, ergosinine, ergotaminine, ergocorninine, ergocryptinine, and ergocristinine. A reliable, sensitive, and accurate multiple mycotoxin method, based on extraction with a Mycosep 150 multifunctional column prior to analysis using UHPLC-MS/MS, was validated using samples of swine feed (100) and dairy feed (100) for the 11 targeted EAs. Based on the obtained validation results, this method showed good performance recovery and inter-day and intra-day precision that are in accordance with standard criteria to ensure reliable occurrence data on EA contaminants. More than 49% of the swine feed samples were contaminated with EAs, especially ergocryptine(-ine) (40%) and ergosine (-ine) and ergotamine (-ine) (37%). However, many of the 11 EAs were not detectable in any swine feed samples. In addition, there were contaminated (positive) dairy feed samples, especially for ergocryptine (-ine) (50%), ergosine (-ine) (48%), ergotamine (-ine), and ergocristine (-ine) (49%). The mycotoxin levels in the feed samples in this study almost complied with the European Union regulations.

To date, the necessary pharmacokinetic information has been limited to establish suitable therapeutic plans for freshwater crocodiles. Therefore, this study was conducted to evaluate the pharmacokinetic profile of the oxytetracycline long-acting formulation (OTC-LA) in the freshwater crocodile, Crocodylus siamensis, following a single intramuscular (i.m.) administration at three different dosages of 5, 10 and 20 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 216 h after i.m. administration at the three different dosages. The plasma concentrations of OTC were measured using a validated liquid chromatography tandem-mass spectrometry (LC-MS/MS) method. The C_max (± SD) values of OTC were 2.15 ± 0.51 µg/mL, 7.68 ± 1.08 µg/mL and 17.08 ± 2.09 µg/mL at doses of 5, 10 and 20 mg/kg b.w., respectively. The elimination half-life values were 33.59 ± 2.51 h, 38.42 ± 5.47 h and 38.04 ± 1.98 h at dosages of 5, 10 and 20 mg/kg b.w., respectively. Based on the pharmacokinetic data, the pharmacokinetic/pharmacodynamic (PK/PD) index, the susceptibility break-point and plasma protein binding, a dosage once every two weeks of 10 mg/kg b.w. OTC intramuscularly might be suitable for initiating the treatment of susceptible bacterial infections in freshwater crocodiles. However, further PK/PD studies are warranted to confirm whether the dose rates used in this study can produce longer-term antimicrobial success for diseases caused by susceptible bacteria in freshwater crocodiles.

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.

Poapolathep A, et al. J Vet Sci. 2024 Jul;25(4):e58. https://doi.org/10.4142/jvs.24118

Florfenicol (FFC) is widely used to treat bacterial infections in veterinary medicine; however, its pharmacokinetic characteristics in reptiles remain limited. This study investigated the pharmacokinetic profiles of FFC after intramuscular (IM) injection at doses of 20 or 30 mg/kg body weight (b.w.) in freshwater crocodiles (Crocodylus siamensis). A sample of 10 healthy crocodiles was randomly divided into two groups (n = 5 for each group) according to a parallel study design. Blood samples were obtained from pre-dose to 168 h post-administration. Plasma FFC concentrations were quantified using high-performance liquid chromatography with diode array detection (HPLC-DAD) and analyzed by non-compartmental analysis. The mean maximum plasma concentrations of FFC were 4.05 µg/mL and 6.11 µg/mL for the 20 and 30 mg/kg b.w. doses, respectively. The mean elimination half-lives of FFC were long but not significantly different (51 h). The average plasma protein binding was 37.15%. Based on the pharmacokinetics/pharmacodynamics (PK/PD) index, a single dose of FFC via IM elicited plasma concentrations above the MIC₉₀ values reported for several susceptible bacterial pathogens. Consequently, both dose levels provided plasma exposure consistent with previously reported reference MIC values. However, further PK/PD and multiple-dose investigations are needed to refine species-specific dosage regimens.