Elena Badillo

Doramectin (DRM) is a broad-spectrum macrocyclic lactone antiparasitic agent widely used in veterinary medicine. Its pharmacokinetics in reptiles, particularly Siamese freshwater crocodiles (Crocodylus siamensis), remain limited. This study aimed to characterize the pharmacokinetic profiles of DRM following subcutaneous (SC) and intramuscular (IM) administration in Siamese crocodiles. Twenty clinically healthy male crocodiles were randomly allocated into four groups (n = 5 per group) and administered a single dose of DRM at 0.2 or 0.3 mg/kg body weight (b.w.) via either the SC or IM route. Blood samples were collected from pre-dose to 60 days after administration, and plasma DRM concentrations were quantified using a validated high-performance liquid chromatography method with fluorescence detector. Pharmacokinetic parameters were determined by non-compartmental analysis. Plasma DRM concentrations remained quantifiable through day 60 in 19 of 20 animals. Geometric mean maximum plasma concentrations (C_max) were 14.73 and 20.28 ng/mL following SC administration at 0.2 and 0.3 mg/kg, respectively, and 24.48 and 36.34 ng/mL following IM administration. Significantly higher C_max values were observed at 0.3 mg/kg for both routes (p < 0.05). Median T_max values were 11 and 9 days following SC administration and 3 and 4 days following IM administration at 0.2 and 0.3 mg/kg, respectively. The geometric mean terminal elimination half-lives (T_1/2λz) were 5.37 and 9.73 days for SC administration and 7.38 and 9.97 days for IM administration at 0.2 and 0.3 mg/kg, respectively. Systemic exposure increased with dose. The geometric mean AUC_0–last increased numerically from 368.84 to 491.87 ng × day/mL following SC administration and significantly from 372.45 to 643.97 ng × day/mL following IM administration (p < 0.05). Intramuscular administration resulted in higher C_max and more rapid attainment of peak plasma concentrations than SC administration. These findings demonstrate prolonged systemic persistence and dose-related pharmacokinetic changes in DRM in freshwater crocodiles and provide species-specific information to support further evaluation of dosage regimens.

The aim of this research was to determine the effect of different anesthesia protocols on the pharmacokinetics of tolfenamic acid in cats undergoing ovariohysterectomy. The research involved 12 cats that underwent ovariohysterectomy. The cats were randomly divided into two equal groups: one (n = 6) receiving xylazine–ketamine and the other (n = 6) receiving propofol–isoflurane anesthesia. Tolfenamic acid was administered subcutaneously at a dose of 4 mg/kg 30 min prior to ovariohysterectomy in both groups. The plasma samples were analyzed for tolfenamic acid using high-performance liquid chromatography (HPLC)-UV. The terminal elimination half-life (t_1/2λz), area under the curve (AUC_0-last), maximum plasma concentration (C_max), and time to reach peak plasma concentration (T_max) values after xylazine–ketamine anesthesia were determined to be 3.30 h, 42.17 h*µg/mL, 6.34 µg/mL, and 2 h, respectively. Tolfenamic acid in the propofol–isoflurane anesthetic group showed shorter t_1/2λz and T_max than the xylazine–ketamine group but a greater C_max. However, AUC_0-last was similar in both anesthesia groups. These results showed that the pharmacokinetics of tolfenamic acid may vary depending on the anesthesia protocol used in ovariohysterectomy. However, there is a need to evaluate the efficacy of tolfenamic acid in cats under both anesthesia regimens.

The influence of the state of pregnancy (days 45, 90, and 135 of gestation) on the pharmacokinetics of levamisole was investigated in ewes. Twelve healthy Merino female sheep were allocated into two groups ( n = 6 per group). The ewes in group 1 (non‐pregnant) were not mated, while the ewes in group 2 (pregnant) were mated with rams by synchronizing their estrus cycles. Levamisole was injected intramuscularly once at a dose of 7.5 mg/kg into all ewes. Blood samples were taken at 13 different times over a 48‐h period according to a defined protocol. Plasma samples were analyzed for levamisole via high‐performance liquid chromatography. Pregnant ewes had significantly lower C _max , AUC _0‐last , and t _1/2ʎz of levamisole than non‐pregnant ewes. There were no significant differences in T _max between the two groups. The values of AUC _0‐last , C _max , and t _1/2ʎz decreased as pregnancy progressed. These results indicated that pregnancy reduced exposure (AUC _0‐last ) and duration of levamisole presence in the body. This information contributes to the use of levamisole in pregnant ewes, but further studies are needed to determine the change in therapeutic effect related to pregnancy.

This study investigated age-related variations in the pharmacokinetics of enrofloxacin and its active metabolite, ciprofloxacin, in calves. This study was carried out on a total of 18 calves using a parallel pharmacokinetic design. Eighteen animals were assigned to three age groups, one, four, and eight months old, and received a single intravenous dose of 10 mg/kg enrofloxacin. Serial blood samples collected over 48 h were analyzed using high-performance liquid chromatography to determine plasma concentrations. In one-month-old calves, the pharmacokinetic parameters revealed a volume of distribution at steady state (V_dss) of 1.44 L/kg, total clearance (Cl_T) of 0.42 L/h/kg, elimination half-life (t_1/2ʎz) of 2.52 h, and area under the concentration versus time curve (AUC_0-last) of 23.36 h*μg/mL. Notably, the AUC_0-last of enrofloxacin was increased and Cl_T decreased in the older age groups (four and eight months). Additionally, the V_dss of enrofloxacin significantly decreased in eight-month-old calves relative to younger groups, while t_1/2ʎz showed statistically significant differences in the order of four months > eight months > one month. The conversion ratio of enrofloxacin to ciprofloxacin was highest in one-month-old calves (43.39%) and diminished in four-month-old (25.73%) and eight-month-old (23.04%) calves. The results indicated that the pharmacokinetics of enrofloxacin and ciprofloxacin at a dose of 10 mg/kg in cattle exhibited significant variation with age. However, pharmacokinetic/pharmacodynamic investigations in cattle of different ages are required to assess the impact of these pharmacokinetic alterations on clinical efficacy.

The growing occurrence of emerging contaminants, particularly pharmaceutical residues, in aquatic environments represents a major environmental concern worldwide. While pharmaceutical contamination has been increasingly studied in marine systems, port environments remain largely understudied despite their complex anthropogenic pressures. This study investigates the occurrence, spatial distribution, and potential environmental risk of pharmaceutical residues in surface waters of the port of Cartagena, a multifunctional port on the Spanish Mediterranean coast. Fifteen pharmaceuticals were analysed across nine sampling sites, of which six were not detected. Diclofenac and several antibiotics (erythromycin, azithromycin, clindamycin, and trimethoprim) were the most frequently detected compounds, reaching maximum concentrations of up to 12,294.1 ng/L. Elevated concentrations were observed at sites associated with intense human activity, while the detection of multiple pharmaceuticals at a designated Special Area of Conservation suggests additional diffuse pollution sources, likely linked to insufficient wastewater management in nearby informal settlements. Most detected concentrations exceeded established environmental-quality or risk-threshold values, indicating a potential threat to marine ecosystems. These findings highlight the vulnerability of port environments to pharmaceutical pollution and underscore the need for continuous monitoring programs to support effective environmental management and biodiversity protection in coastal port areas.

Purpose: Selective oestrogen receptor modulators (SERMs) are a standard treatment for breast cancer and osteoporosis. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is a serious public health concern. This study aimed to identify potential pharmacovigilance signals related to dementia and AD for SERMs in menopausal and postmenopausal women. Methods: To investigate this possible association, a disproportionality analysis was performed in VigiBase, the World Health Organization’s (WHO) global database of individual case safety reports (ICSRs). Disproportionality was quantified using the reporting odds ratio (ROR). Results: We found risk of reporting dementia for tamoxifen [ROR = 1.74 (1.23–2.45)] and raloxifene [ROR = 1.63 (1.05–2.53)] and AD for raloxifene [ROR = 5.12 (3.26–8.05)]. No statistically significant association was detected for fulvestrant and bazedoxifene with dementia or AD. Most of the reports were severe and affected women over the age of 75. The latency of the reactions was predominantly long, suggesting that dementia is a late-onset reaction. The duration of treatment varied from a few months to more than three years, which may indicate that long-term exposure to SERMs is not necessary to develop dementia associated with these drugs. Conclusion: Signals of disproportionate reporting have been observed between the incidence of dementia and AD with SERMs. There are conflicting results from the different studies that have been conducted on the relationship between these drugs and AD. More research is needed to find out what factors determine the risk of cognitive impairment associated with SERMs.

Background/Objectives: The aim of this study was to determine the plasma and muscle pharmacokinetics of ceftriaxone (25 mg/kg) in tilapia after different administration routes. Methods: Two hundred and sixteen fish maintained at 30 ± 1.5 °C were divided equally into three treatment groups: intravascular (IV), intraperitoneal (IP), and intramuscular (IM). Ceftriaxone concentrations were quantified using high-performance liquid chromatography, and pharmacokinetic parameters were calculated by non-compartmental analysis. Results: The plasma total body clearance, volume of distribution at steady state, and elimination half-life (t_1/2λz) were 0.22 L/h/kg, 0.85 L/kg, and 5.27 h, respectively. The t_1/2λz values were comparable among the IV, IP, and IM injection groups. The peak plasma concentration was 37.71 ± 3.12 µg/mL and 40.51 ± 2.77 µg/mL following IP and IM injection, respectively. The bioavailability was 67.04% for IP and 101.48% for IM. The peak muscle concentration was 9.49 ± 0.75 µg/g for IV, 5.71 ± 0.85 µg/g for IP, and 12.24 ± 2.41 µg/g for IM injection. The AUC_{0–∞muscle}/AUC_{0–∞plasma} ratio was 0.23, 0.18, and 0.30 for the IV, IP, and IM groups, respectively. The AUC_muscle/AUC_plasma indicates the ratio of drug penetration into the muscle, and a value less than 1 indicates that ceftriaxone penetrates into muscle tissue at a low ratio. Conclusions: These results indicate that ceftriaxone is well absorbed after IP and IM injections and passes into muscle tissue at a low tissue penetration. Ceftriaxone can be administered via IP and IM injection in Nile tilapia; nevertheless, its therapeutic efficacy requires evaluation.

This study aimed to examine the pharmacokinetic changes in tolfenamic acid administered intravenously and orally to ducks at different doses (2, 4, and 8 mg/kg). Furthermore, the binding ratio to plasma proteins was assessed utilizing the ultrafiltration method. Eighteen male Pekin ducks were randomly assigned to three dosage groups (2, 4, and 8 mg/kg), with each group undergoing a trial in two phases: intravenous (IV) and oral administration. The sample was analyzed using an approved HPLC-UV method. A non-compartmental analysis was utilized to evaluate the pharmacokinetic data. For 2 mg/kg IV injection, the area under the curve from zero to infinity (AUC_0-∞), total clearance (Cl_T), volume of distribution at steady state (V_dss), and elimination half-life (t_1/2ʎz) were 13.03 h*µg/mL, 0.15 L/h/kg, 0.30 L/kg, and 1.72 h, respectively. Following oral administration at a dose of 2 mg/kg, the AUC_0-∞, peak plasma concentration (C_max), and bioavailability were 6.32 h*µg/mL, 2.25 µg/mL, and 48.52%, respectively. The t_1/2ʎz was extended, C_max and AUC_0-∞ elevated, T_max shortened, and Cl_T decreased in a dose-dependent manner. No dose-related change was observed in V_dss and bioavailability. In ducks, tolfenamic acid’s plasma protein binding was 99.74%, unaffected by concentration. These results may contribute to the application of tolfenamic acid in ducks at different doses, but dose-related changes in therapeutic efficacy should also be demonstrated.

This review aims to provide an overview of the pharmacokinetics of antibiotics in crocodilian species, focusing on species-specific variations in drug absorption, distribution, metabolism, and elimination (ADME), as well as the influence of environmental factors. A review of the available literature across crocodilian species reveals notable pharmacokinetic variability. Environmental influences, such as temperature and metabolic rate, are shown to impact these pharmacokinetic parameters significantly. Despite the frequent use of antibiotics in clinical and conservation settings, the lack of standardized dosing regimens presents risks of under- or over-dosing. This variability is compounded by limited research on species-specific drug metabolism and elimination processes. The review highlights the need for further pharmacokinetic studies to develop evidence-based dosing protocols, optimize therapeutic outcomes, and address concerns related to antimicrobial resistance. Future research should focus on filling the gaps in PK data to refine dosing strategies and ensure both efficacy and safety in crocodilian species.