Doxycycline is a second-generation tetracycline, marketed in different species for treating infections caused by susceptible bacteria. Little information is available on the pharmacokinetics of doxycycline in lactating goats. The objective of this study was to establish the disposition kinetics of doxycycline after parenteral administration (intravenous and intramuscular) in dairy goats and its elimination in milk. A cross-over model was designed (n = 6). Doxycycline was dosed at 5 mg/kg for intravenous administration and 20 mg/kg for extravascular administrations. Noncompartmental pharmacokinetic methods were used to calculate plasma concentration–time data. The V_z value suggests a moderate distribution of this antibiotic in goats, with a value of 0.85 L/kg. A low bioavailability (F = 45.60%) of doxycycline following an intramuscular injection was observed, with all animals exhibiting signs of lameness. Doxycycline rapidly crossed the blood–milk barrier, but exposure to the antimicrobial and the concentrations reached in milk were lower than those obtained in plasma. Although PK/PD ratios may be low with the pharmacokinetic data obtained with this formulation of doxycycline, at this dose and route of administration, doxycycline after IM administration could be useful for infections by moderate or highly susceptible bacteria in the mammary gland of goats. However, it may be necessary to test different doses of doxycycline or other routes of administration to achieve better surrogate markers and to establish repeated dosing regimens and clinical efficacy.

Danofloxacin is a fluoroquinolone antibiotic approved for use in fish. It can be used for bacterial infections in fish of all body sizes. However, physiological differences in fish depending on size may change the pharmacokinetics of danofloxacin and therefore its therapeutic efficacy. In this study, the change in the pharmacokinetics of danofloxacin in rainbow trout of various body sizes was revealed for the first time. The objective of this investigation was to compare the plasma and tissue pharmacokinetics of danofloxacin in rainbow trout of different body sizes. The study was conducted at 14 ± 0.5 °C in fish of small, medium, and large body size and danofloxacin was administered orally at a dose of 10 mg/kg. Concentrations of this antimicrobial in tissues and plasma were quantified by high performance liquid chromatography with ultraviolet detector. The plasma elimination half-life (t_1/2ʎz), volume of distribution (V_darea/F), total clearance (CL/F), peak concentration (C_max), and area under the plasma concentration–time curve (AUC_0–last) were 27.42 h, 4.65 L/kg, 0.12 L/h/kg, 2.53 µg/mL, and 82.46 h·µg/mL, respectively. Plasma t_1/2ʎz, AUC_0–last and C_max increased concomitantly with trout growth, whereas CL/F and V_darea/F decreased. Concentrations in liver, kidney, and muscle tissues were higher than in plasma. C_max and AUC_0–last were significantly higher in large sizes compared to small and medium sizes in all tissues. The scaling factor in small, medium, and large fish was 1.0 for bacteria with MIC thresholds of 0.57, 0.79, and 1.01 µg/mL, respectively. These results show that therapeutic efficacy increases with body size. However, since increases in danofloxacin concentration in tissues of large fish may affect withdrawal time, attention should be paid to the risk of tissue residue.

Doxycycline is an antimicrobial agent used in veterinary medicine to treat a variety of bacterial infections. To date, no analytical technique utilising HPLC with fluorescence detection has been documented for the quantification of doxycycline concentrations in goat plasma or milk. Consequently, the objective of the present study was to propose a rapid HPLC assay with fluorescence detection for the quantification of doxycycline in the aforementioned samples, thereby facilitating the conduct of pharmacokinetic studies and the detection of residues in diverse goat tissues. Proteins were precipitated with methanol and trifluoroacetic acid in a single step. Doxycycline was separated on a XBRIDGE C18 column using an isocratic method. Sample volume injected into the HPLC system was 50 µl. Fluorescence detection was conducted with an excitation wavelength of 380 nm and an emission wavelength of 520 nm. The retention times of doxycycline and danofloxacin (internal standard) were determined to be 8.0 and 5.5 minutes, respectively. The calibration curves for plasma and milk exhibited linearity over the concentration range of 0.1 to 2 μg/mL. The limit of detection was 0.065 μg/ mL, while the limit of quantification was 0.1 μg/mL in both matrices. The accuracy and precision of the method were consistently within the limits of 10.9% for plasma and 10.5% for milk. The findings of this study may be employed in the quantification of doxycycline in goat plasma and milk, thus facilitating the conduct of pharmacokinetic studies.

Background/Objectives: Doxycycline, a tetracycline-class antibiotic, is commonly used across various species to treat infections caused by susceptible bacteria. However, pharmacokinetic data on its use in alpacas remains limited. This study aimed to investigate the pharmacokinetics of doxycycline following intravenous (IV) and subcutaneous (SC) administration in alpacas. Methods: A randomized crossover study (n = 6) was employed, with dosages of 5 mg/kg and 20 mg/kg after intravenous and subcutaneous administration, respectively. Blood samples were collected at predetermined times up to 96 h after both routes of administration. Plasma doxycycline concentrations were determined using validated high-performance liquid chromatography with a UV detector and then analyzed based on non-compartmental pharmacokinetic methods. Results: All alpacas maintained optimal health and general condition throughout the trial period. After intravenous administration, the V_z value (0.90 L/kg) indicated a good distribution of this antibiotic in the alpacas. The maximum concentration value (C_max) after SC administration of doxycycline was 1.40 µg/mL, reached at 1.92 h. Low bioavailability (F = 36.83%) of doxycycline was observed after SC administration. Conclusions: PK/PD ratios calculated from the pharmacokinetic data obtained, at a dose of 20 mg/kg and SC route of administration, suggest that doxycycline administered every 24 h could be effective against bacterial infections with MICs of 0.125 and 0.5 µg/mL. However, multi-dose and pharmacodynamic studies are needed to further evaluate the efficacy of using doxycycline in alpacas.

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.

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.