Pharmacokinetics of enrofloxacin after oral,intramuscular and bath administration in crucian carp (Carassius auratus gibelio)

The pharmacokinetics of enrofloxacin (ENR) was studied in crucian carp (Carassius auratus gibelio) after single administration by intramuscular (IM) injection and oral gavage (PO) at a dose of 10 mg/kg body weight and by 5 mg/L bath for 5 hr at 25°C. The plasma concentrations of ENR and ciprofloxacin (CIP) were determined by HPLC. Pharmacokinetic parameters were calculated based on mean ENR or CIP concentrations using WinNonlin 6.1 software. After IM, PO and bath administration, the maximum plasma concentration (C_max) of 2.29, 3.24 and 0.36 μg/ml was obtained at 4.08, 0.68 and 0 hr, respectively; the elimination half‐life (T_1/2β) was 80.95, 62.17 and 61.15 hr, respectively; the area under the concentration–time curve (AUC) values were 223.46, 162.72 and 14.91 μg hr/ml, respectively. CIP, an active metabolite of enrofloxacin, was detected and measured after all methods of drug administration except bath. It is possible and practical to obtain therapeutic blood concentrations of enrofloxacin in the crucian carp using IM, PO and bath immersion administration.     

Pharmacokinetics of florfenicol and thiamphenicol in ducks

The pharmacokinetics of florfenicol (FF) and thiamphenicol (TP) after single intravenous (IV) and oral (PO) administration was investigated in Mulard ducks. Both antibiotics were administered at a dose of 30 mg/kg body weight, and their concentrations in plasma samples were assayed using high‐performance liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were calculated using a noncompartmental method. After IV administration, significant differences were found for the mean residence time (2.25 ± 0.21 hr vs. 2.83 ± 0.50 hr for FF and TP, respectively) and the general half‐life (1.56 ± 0.15 hr vs. 1.96 ± 0.35 hr for FF and TP, respectively) indicating slightly slower elimination of TP as compared to FF. The clearance, however, was comparable (0.30 ± 0.07 L/hr/kg for FF and 0.26 ± 0.04 L/hr/kg for TP). The mean volume of distribution was below 0.7 L/kg for both drugs. Pharmacokinetics after PO administration was very similar for FF and TP suggesting minor clinical importance of the differences found in the IV study. Both antimicrobials showed rapid absorption and bioavailability of more than 70% indicating that PO route should be an efficient method of FF and TP administration to ducks under field conditions.     

Plasma concentrations of itraconazole following a single oral dose in juvenile California sea lions (Zalophus californianus)

The objective of this study was to establish a single-dose pharmacokinetic profile for orally administered itraconazole in California sea lions (Zalophus californianus). Twenty healthy rehabilitated juvenile California sea lions were included in this study. Itraconazole capsules were administered orally with food at a target dose of 5–10 mg/kg. Blood samples were collected from each animal at 0 hr and at two of the following timepoints: 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 hr. Quantitative analysis of itraconazole in plasma samples was performed by high-performance liquid chromatography. An average maximum concentration of 0.22 µg/ml ± 0.11 was detected 4 hr after administration. The average concentration fell to 0.12 µg/ml ± 0.11 by 6 hr and 0.02 µg/ml ± 0.02 at 12 hr. At no point did concentrations reach 0.5 µg/ml, the concentration commonly accepted for therapeutic efficacy. While this formulation was well tolerated by the sea lions, oral absorption was poor and highly variable among individuals. These data indicate that a single oral dose of itraconazole given as a capsule at 5–10 mg/kg, under the conditions used in this study, does not achieve therapeutic plasma concentrations in California sea lions.     

The evaluation of lycopene and cysteamine supplementation effects on sperm and oxidative stress parameters during chilled storage of canine semen

The aim of this study was to evaluate the effects of different concentrations of lycopene and cysteamine on characteristics of sperm, liquid peroxidation and enzymatic activities in seminal plasma of canine semen preserved at 5°C for 72 hr. The semen samples were divided into eight aliquots: control, control sham (dimethyl sulfoxide 5%), lycopene groups (250, 500 and 750 µg/ml) and cysteamine groups (2.5, 5 and 10 mM). Motility, viability, membrane integrity, DNA integrity, total antioxidant capacity (TAC) and malondialdehyde (MDA) levels were evaluated. Progressive motility and total motility were higher with the 500 and 750 µg/ml lycopene concentrations, respectively, compared to the control group and the cysteamine groups following 72 hr of storage in the liquid storage. Motility characteristics, viability and hypo-osmotic swelling test (HOST) percentages were significantly improved in 500 µg/ml lycopene compared to other groups. The 500 and 750 µg/ml lycopene concentrations, respectively, showed significantly reduced percentages of spermatozoa with DNA integrity compared to the control group. The 500 and 750 µg/ml lycopene concentrations, respectively, led to the significant decrease of MDA levels. The 500 µg/ml lycopene enhanced TAC levels after 48 and 72 hr that was not observed in other groups. In conclusion, the findings of this study showed that lycopene supplementation in canine semen extenders improved canine semen parameters and TAC levels and decreased MDA levels in the chilling process.     

Pharmacokinetics of florfenicol and its metabolite florfenicol amine in crucian carp (Carassius auratus) at three temperatures after one single intramuscular injection

The pharmacokinetic profiles of florfenicol (FF) or florfenicol amine (FFA) in crucian carp were compared at different water temperatures after single intramuscular administration of FF at 10 mg/kg bodyweight. The concentrations of FF and FFA were determined by a high‐performance liquid chromatography method, and then, the concentration versus time data were subjected to compartmental analysis using a one‐compartment open model. At the water temperatures of 10, 20, and 25°C, the peak concentrations (C_maxs) of FF were 2.28, 2.29, and 2.34 μg/ml, respectively, while those of FFA were 0.42, 0.71, and 0.82 μg/ml, respectively. And the absorption half‐life (t_1/2ka) of FF was 0.21, 0.19, and 0.21 hr, while the elimination half‐life (t_1/2kel) was 31.66, 24.77, and 21.48 hr, respectively. For FFA, the formation half‐life (t_1/2kf) was 3.85, 8.97, and 12.43 hr, while the t_1/2kel was 58.34, 30.27, and 21.22 hr, respectively. The results presented here demonstrated that the water temperature had effects on the elimination of both FF and FFA and the formation of FFA. Based on the T > MIC values calculated here, to treat the infections of bacterial with MIC value ≤ 0.5 μg/ml, FF intramuscularly given at 10 mg/kg bodyweight with a 72‐hr interval is sufficient at the water temperature of 10°C, while the intervals of 60 and 48 hr were needed at 20 and 25°C, respectively. But to treat bacterial with higher MIC values, more FF or FF at 10 mg/kg BW but with shorter intervals should be intramuscularly given to the infected fish.     

Effect of ketoprofen co-administration on pharmacokinetics of cefquinome following repeated administration in goats

The pharmacokinetics of cefquinome (2 mg/kg every 24 hr for 5 days) was determined following intramuscular administration alone and co-administration with ketoprofen (3 mg/kg every 24 hr for 5 days) in goats. Six goats were used for the study. In the study, the crossover pharmacokinetics design with 20-day washout period was performed in two periods. Plasma concentrations of cefquinome were assayed using high-performance liquid chromatography by ultraviolet detection. The mean terminal elimination half-life (t_1/2ʎz), area under the concentration–time curve (AUC_0–24), peak concentration (C_max), apparent volume of distribution (V_darea/F), and total body clearance (CL/F) of cefquinome after the administration alone were 4.85 hr, 11.06 hr*µg/ml, 2.37 µg/mL, 1.23 L/kg, and 0.17 L/h/kg after the first dose, and 5.88 hr, 17.01 hr*µg/mL, 3.04 µg/mL, 0.95 L/kg, and 0.11 L/h/kg after the last dose. Ketoprofen significantly prolonged t_1/2ʎz of cefquinome, increased AUC_0–24 and C_max, and decreased V_darea/F and CL/F. Cefquinome exhibited low accumulation after the administration alone and in combination with ketoprofen. These results indicated that ketoprofen prolonged the elimination of cefquinome in goats. The 24-hr dosing intervals at 2 mg/kg dose of cefquinome, which co-administered with ketoprofen, may maintain T> minimum inhibitory concentration (MIC) values above 40% in the treatment of infections caused by susceptible pathogens with the MIC value of ≤0.75 μg/ml in goats with an inflammatory condition.     

Pharmacokinetics and tissue concentrations of firocoxib in sows following oral administration

The objectives of this study were to describe the pharmacokinetics of firocoxib following oral (PO) dosing and intravenous (IV) injection in sows. Seven healthy sows were administered 0.5 mg firocoxib/kg IV. Following a 23-d washout period, sows were administered firocoxib at 4.0 mg firocoxib/kg PO. Blood samples were collected at predetermined times for 72 hr after IV and 120 hr after PO administration. Plasma firocoxib concentration was measured using UPLC-MS/MS, and pharmacokinetic analysis was performed using noncompartmental procedures. Tissue firocoxib concentrations were determined at 5, 10 (n = 2/time point), and 21 d (n = 3) after PO administration. The geometric mean half-life following IV and PO administration was 16.6 and 22.5 hr, respectively. A mean peak plasma concentration (Cmax) of 0.06 µg/ml was recorded at 7.41 hr (T_max) after oral administration. Mean oral bioavailability was determined to be 70.3%. No signs of NSAID toxicity were observed on macroscopic and microscopic investigation. Firocoxib was detected in the skin with subcutaneous fat (0.02 µg/g) of one of three sows at 21 days postadministration. Additional work to establish appropriate meat withhold intervals in sows is required. Firocoxib was readily absorbed following PO administration. Further work is needed to better understand the analgesic effects for sows and piglets nursing sows administered firocoxib.     

Effects of electroporation treatment using different concentrations of Cas9 protein with gRNA targeting Myostatin (MSTN) genes on the development and gene editing of porcine zygotes

This study was conducted to investigate the effect of seven concentrations of Cas9 protein (0, 25, 50, 100, 200, 500, and 1,000 ng/µl) on the development and gene editing of porcine embryos. This included the target editing and off‐target effect of embryos developed from zygotes that were edited via electroporation of the Cas9 protein with guide RNA targeting Myostatin genes. We found that the development to blastocysts of electroporated zygotes was not affected by the concentration of Cas9 protein. Although the editing rate, which was defined as the ratio of edited blastocysts to total examined blastocysts, did not differ with Cas9 protein concentration, the editing efficiency, which was defined as the frequency of indel mutations in each edited blastocyst, was significantly decreased in the edited blastocysts from zygotes electroporated with 25 ng/µl of Cas9 protein compared with that of blastocysts from zygotes electroporated with higher Cas9 protein concentrations. Moreover the frequency of indel events at the two possible off‐target sites was not significantly different with different concentrations of Cas9 protein. These results indicate that the concentration of Cas9 protein affects gene editing efficiency in embryos but not the embryonic development, gene editing rate, and non‐specific cleavage of off‐target sites.     

Pharmacokinetics of cefquinome in crucian carp (Carassius auratus gibelio) after oral,intramuscular, intraperitoneal,and bath administration

The pharmacokinetics (PK) of cefquinome (CEQ) was studied in crucian carp (Carassius auratus gibelio) after single oral, intramuscular (i.m.), and intraperitoneal (i.p.) administration at a dose of 10 mg/kg body weight and following incubation in a 5 mg/L bath for 5 hr at 25°C. The plasma concentration of CEQ was determined using high‐performance liquid chromatography (HPLC). PK parameters were calculated based on mean CEQ concentration using WinNonlin 6.1 software. The disposition of CEQ following oral, i.m., or i.p. administration was best described by a two‐compartment open model with first‐order absorption. After oral, i.m., and i.p. administration, the maximum plasma concentration (C_max) values were 1.52, 40.53, and 67.87 μg/ml obtained at 0.25, 0.23, and 0.35 hr, respectively, while the elimination half‐life (T_1/2β) values were 4.68, 7.39, and 6.88 hr, respectively; the area under the concentration–time curve (AUC) values were 8.61, 339.11, and 495.06 μg hr/ml, respectively. No CEQ was detected in the plasma after bath incubation. Therapeutic blood concentrations of CEQ can be achieved in the crucian carp following i.m. and i.p. administration at a dosage of 10 mg/kg once every 2 days.     

The intravenous pharmacokinetics of butorphanol and detomidine dosed in combination compared with individual dose administrations to exercised horses

In equine and racing practice, detomidine and butorphanol are commonly used in combination for their sedative properties. The aim of the study was to produce detection times to better inform European veterinary surgeons, so that both drugs can be used appropriately under regulatory rules. Three independent groups of 7, 8 and 6 horses, respectively, were given either a single intravenous administration of butorphanol (100 µg/kg), a single intravenous administration of detomidine (10 µg/kg) or a combination of both at 25 (butorphanol) and 10 (detomidine) µg/kg. Plasma and urine concentrations of butorphanol, detomidine and 3-hydroxydetomidine at predetermined time points were measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS). The intravenous pharmacokinetics of butorphanol dosed individually compared with co-administration with detomidine had approximately a twofold larger clearance (646 ± 137 vs. 380 ± 86 ml hr⁻¹ kg⁻¹) but similar terminal half-life (5.21 ± 1.56 vs. 5.43 ± 0.44 hr). Pseudo-steady-state urine to plasma butorphanol concentration ratios were 730 and 560, respectively. The intravenous pharmacokinetics of detomidine dosed as a single administration compared with co-administration with butorphanol had similar clearance (3,278 ± 1,412 vs. 2,519 ± 630 ml hr⁻¹ kg⁻¹) but a slightly shorter terminal half-life (0.57 ± 0.06 vs. 0.70 ± 0.11 hr). Pseudo-steady-state urine to plasma detomidine concentration ratios are 4 and 8, respectively. The 3-hydroxy metabolite of detomidine was detected for at least 35 hr in urine from both the single and co-administrations. Detection times of 72 and 48 hr are recommended for the control of butorphanol and detomidine, respectively, in horseracing and equestrian competitions.     

Comparative pharmacokinetics of florfenicol in healthy and Pasteurella multocida‐infected Gaoyou ducks

Pasteurella multocida is the causative agent of fowl cholera, and florfenicol (FF) has potent antibacterial activity against P. multocida and is widely used in the poultry industry. In this study, we established a P. multocida infection model in ducks and studied the pharmacokinetics of FF in serum and lung tissues after oral administration of 30 mg/kg bodyweight. The maximum concentrations reached (C_max) were lower in infected ducks (13.88 ± 2.70 μg/ml) vs. healthy control animals (17.86 ± 1.57 μg/ml). In contrast, the mean residence time (MRT: 2.35 ± 0.13 vs. 2.27 ± 0.18 hr) and elimination half‐life (T_½β: 1.63 ± 0.08 vs. 1.57 ± 0.12 hr) were similar for healthy and diseased animals, respectively. As a result, the area under the concentration curve for 0–12 hr (AUC_0–12 hr) for FF in healthy ducks was significantly greater than that in infected ducks (49.47 ± 5.31 vs. 34.52 ± 8.29 μg hr/ml). The pharmacokinetic differences of FF in lung tissues between the two groups correlated with the serum pharmacokinetic differences. The C_max and AUC_0–12 hr values of lung tissue in healthy ducks were higher than those in diseased ducks. The concentration of FF in lung tissues was approximately 1.2‐fold higher than that in serum both in infected and healthy ducks indicating that FF is effective in treating respiratory tract infections in ducks.     

Glucose and insulin response after intravenous and subcutaneous somatostatin administration in healthy horses

Equine metabolic syndrome (EMS) is prevalent in the equine population, and somatostatin analogs might be useful for diagnosis and/or treatment of EMS in horses. The purpose of this study was to evaluate the glucose and insulin responses to subcutaneous and intravenous administration of somatostatin. Six healthy research horses were included in this prospective study. An initial pilot study was performed to assess several different doses (10–22 µg/kg [4.5–10 µg/lb]) in two horses, then a final dosage of 22 µg/kg (10 µg/lb) was administered to six horses IV and SQ in a two‐period randomized cross‐over study performed over a 3‐month study period. Blood samples were collected for measurement of plasma insulin and glucose concentrations during a 24‐hr study period. Both IV and SQ somatostatin resulted in decreased insulin and increased glucose concentrations. SQ somatostatin resulted in a longer clinical effect, with return to baseline insulin occurring at 1.5 hr postadministration, versus 45 min for IV. Both IV and SQ administration of somatostatin to normal horses resulted in decreased insulin and increased glucose concentrations, likely due to suppression of insulin secretion by somatostatin. A more prolonged effect was seen following SQ administration as compared to IV administration, and no adverse effects were noted at varying doses. This study provides additional information regarding the effect of somatostatin administration on insulin and glucose concentrations in clinically healthy horses.     

Pharmacokinetic profiles of meloxicam after single IV and PO administration in Bilgorajska geese

The purpose of this study was two-fold: I) to determine the pharmacokinetic profile of meloxicam (MLX) in geese after intravenous (IV) and oral (PO) administration and II) to assess tissue residues in muscle, heart, liver, lung, and kidney. Ten clinically normal female Bilgorajska geese were divided into two groups (treated, n = 8; control, n = 2). Group 1 underwent a 3-phase parallel study with a 1-week washout period. In phase I, animals received MLX (0.5 mg/kg) by IV administration; the blood was collected up to 48 hr. In phases II and III geese were treated orally at the same dosage for the collection of blood and tissue samples, respectively. Group 2 served as control. After the extraction procedure, a validated HPLC method with UV detection was used for plasma and organ analysis. The plasma concentrations were quantifiable up to 24 hr after both the administrations. The elimination phase of MLX from plasma was similar in both the administration groups. The clearance was slow (0.00975 L/hr*Kg), the volume of distribution small (0.0487 L/kg), and the IV half-life was 5.06 ± 2.32 hr. The average absolute PO bioavailability was 64.2 ± 24.0%. Residues of MLX were lower than the LOQ (0.1 µg/kg) in any tested tissue and at any collection time. The dosage used in this study achieved the plasma concentration, which provides analgesia in Hispaniolan Amazon parrots for 5 out of 24 hr after PO administration. MLX tissue concentrations were below the LOD of the assay in tissue (0.03 µg/ml). A more sensitive technique might be necessary to determine likely residue concentrations in tissue.     

Genotyping of Streptococcus agalactiae strains isolated from fish,human and cattle and their virulence potential in Nile tilapia

Streptococcus agalactiae (Lancefield group B; GBS) is a pathogen that causes meningoencephalitis in fish, mastitis in cows, and neonatal sepsis in humans. The objective of this study was to characterize S. agalactiae isolated from fish (n = 27), cows (n = 9), and humans (n = 10) using pulsed-field gel electrophoresis (PFGE) and to investigate the virulence of the identified strains in Nile tilapia (Oreochromis niloticus). The PFGE types were determined by dendogram analyses and the in vivo virulence was evaluated by experimental infection (using i.p. and immersion routes) of Nile tilapia. Among the fish strains, 5 different PFGE patterns were observed and 21 strains showed the same genetic pattern. In some farms two or three profiles occurred simultaneously. The bovine and human strains exhibited high genetic diversity and few relationships were established among S. agalactiae strains from the three host origins analyzed. Eight S. agalactiae strains from fish caused high mortality of Nile tilapia. Three bovine strains infected Nile tilapia (by i.p. route) and two of those strains caused clinical signs of meningoencephalitis. All human strains (n = 5) infected Nile tilapia (by i.p. route) and meningoencephalitis was induced by one strain (by both i.p. and immersion routes). In conclusion, the analyzed strains from the three natural hosts did not show genetic relatedness, yet some of the bovine and human strains were able to infect fish and cause meningoencephalitis. We suggest that genetic linkage is not a prerequisite for S. agalactiae to cross the host-specific barrier.     

Pharmacokinetics,tissue residues,and ex vivo pharmacodynamics of tylosin against Mycoplasma anatis in ducks

The pharmacokinetics of tylosin were investigated in 3 groups of ducks (n = 6). They received a single dose of tylosin (50 mg/kg) by intravenous (IV), intramuscular (IM), and oral administrations, respectively. Plasma samples were collected at various time points to 24 hr post-administration to evaluate tylosin concentration over time. Additionally, tylosin residues in tissues and its withdrawal time were assessed using 30 ducks which received tylosin orally (50 mg/kg) once daily for 5 consecutive days. After IV administration, the volume of distribution, elimination half-life, area under the plasma concentration–time curve, and the total body clearance were 7.07 ± 1.98 L/kg, 2.04 hr, 19.47 µg hr/ml, and 2.82 L hr⁻¹ kg⁻¹, respectively. After IM and oral administrations, the maximum plasma concentrations were 3.70 and 2.75 µg/ml achieved at 1 and 2 hr, and the bioavailability was 93.95% and 75.77%, respectively. The calculated withdrawal periods of tylosin were 13, 8, and 5 days for kidney, liver, and muscle, respectively. For the pharmacodynamic profile, the minimum inhibitory concentration for tylosin against M. anatis strain 1,340 was 1 µg/ml. The calculated optimal oral dose of tylosin against M. anatis in ducks based on the ex vivo pharmacokinetic/pharmacodynamic modeling was 61 mg kg⁻¹ day⁻¹.     

Pharmacokinetic–pharmacodynamic relationship of marbofloxacin for Escherichia coli and Pasturella multocida following repeated intramuscular administration in goats

The pharmacokinetics (PK) and pharmacodynamics (PD) of marbofloxacin (MBF) were determined in six healthy female goats of age 1.00–1.25 years after repeated administration of MBF. The MBF was administered intramuscularly (IM) at 2 mg kg^?1 day^?1 for 5 days. Plasma concentrations of MBF were determined by high‐performance liquid chromatography, and PK parameters were obtained using noncompartmental analysis. The MBF concentrations peaked at 1 hr, and peak concentration (C_max) was 1.760 µg/ml on day 1 and 1.817 µg/ml on day 5. Repeated dosing of MBF caused no significant change in PK parameters except area under curve (AUC) between day 1 (AUC_0–∞D1 = 7.67 ± 0.719 µg × hr/ml) and day 5 (AUC_0‐∞D5 = 8.70 ± 0.857 µg × hr/ml). A slight difference in mean residence time between 1st and 5th day of administration and accumulation index (AI = 1.13 ± 0.017) suggested lack of drug accumulation following repeated IM administration up to 5 days. Minimum inhibitory concentration (MIC) demonstrated that Escherichia coli (MIC = 0.04 µg/ml) and Pasturella multocida (MIC = 0.05 µg/ml) were highly sensitive to MBF. Time‐kill kinetics demonstrated rapid and concentration‐dependent activity of MBF against these pathogens. PK/PD integration of data for E. coli and P. multocida, using efficacy indices: C_max/MIC and AUC_0–24hr/MIC, suggested that IM administration of MBF at a dose of 2 mg kg^?1 day^?1 is appropriate to treat infections caused by E. coli. However, a dose of 5 mg kg^?1 day^?1 is recommended to treat pneumonia caused by P. multocida in goats. The study indicated that MBF can be used repeatedly at dosage of 2 mg/kg in goats without risk of drug accumulation up to 5 days.     

Pharmacokinetics and relative bioavailability of meloxicam oil suspension in pigs after intramuscular administration

This study aimed to develop one novel meloxicam (MEL) oil suspension for sustained-release and compare the pharmacokinetic characteristics of it with MEL conventional formulation in pigs after a single intramuscular administration. Six healthy pigs were used for the study by a crossover design in two periods with a withdrawal interval of 14 days. Plasma concentrations of MEL were measured by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetic parameters were calculated by noncompartmental methods. The difference was statistically significant (p < .05) between MEL oil suspension and MEL conventional formulation in pharmacokinetic parameters of mean residence time (6.16 ± 4.04) hr versus (2.66 ± 0.55) hr, peak plasma concentration (C_max) (0.82 ± 0.12) µg/ml versus (1.12 ± 0.22) µg/ml, time needed to reach C_max (T_max) (2.33 ± 0.82) hr versus (0.59 ± 0.18) hr, and terminal elimination half-life (t_1/2λz) (3.74 ± 2.66) hr versus (1.55 ± 0.37) hr. The mean area under the concentration–time curve (AUC_0–∝) of MEL oil suspension and MEL conventional formulation was 5.35 and 3.43 hr µg/ml, respectively, with a relative bioavailability of 155.98%. Results of the present study demonstrated that the MEL oil suspension could prolong the effective time of drugs in blood, thereby reducing the frequency of administration on a course of treatment. Therefore, the novel MEL oil suspension seems to be of great value in veterinary clinical application.     

Production of Oocytes of Nile Tilapia (Oreochromis niloticus) for In Vitro Fertilization via Hormonal Treatments

Only a few studies have described hormonal treatments for induction of synchronicity and gamete collection in Nile tilapia (Oreochromis niloticus), both important for assortative matings in breeding programmes and essential for polyploidy technologies. In this study, we compared the effectiveness of carp pituitary extract (CPE), Nile tilapia pituitary extract (TPE), human chorionic gonadotropin (hCG) and gonadotropin‐releasing hormone (GnRH) protocols on the induction of spawning and egg production in Nile tilapia. Among the hormonal treatments analysed, only hCG was effective for producing viable gametes for in vitro fertilization. To verify the viability of this hormonal treatment, hCG was tested using different doses (1000, 2000, 3000, 4000 and 5000 IU/kg) in a large number of females (208 animals) from two Nile tilapia lines. The results indicated that hCG doses between 1000 and 5000 IU/kg could be used to induce final oocyte maturation in Nile tilapia with collection of stripped oocytes. This is the first study to report differential reproductive responses to hormonal treatment between tilapia lines: line 1 was more efficient at producing eggs and post‐hatching larvae after hCG induction than line 2. In conclusion, we demonstrated that the hCG protocol may be applied on a large scale to induce final oocyte maturation in Nile tilapia. The development of a protocol for in vitro fertilization in Nile tilapia may aid in breeding programmes and biotechnological assays for the development of genetically modified lines of Nile tilapia.     

Pharmacokinetics and pharmacodynamics of intravenous and transdermal flunixin meglumine in alpacas

The aim of this study was to determine the pharmacokinetics and prostaglandin E₂ (PGE₂) synthesis inhibiting effects of intravenous (IV) and transdermal (TD) flunixin meglumine in eight, adult, female, Huacaya alpacas. A dose of 2.2 mg/kg administered IV and 3.3 mg/kg administered TD using a cross‐over design. Plasma flunixin concentrations were measured by LC‐MS/MS. Prostaglandin E₂ concentrations were determined using a commercially available ELISA. Pharmacokinetic (PK) analysis was performed using noncompartmental methods. Plasma PGE₂ concentrations decreased after IV flunixin meglumine administration but there was minimal change after TD application. Mean t_1/2λz after IV administration was 4.531 hr (range 3.355 to 5.571 hr) resulting from a mean Vz of 570.6 ml/kg (range, 387.3 to 1,142 ml/kg) and plasma clearance of 87.26 ml kg^?1 hr^?1 (range, 55.45–179.3 ml kg^?1 hr^?1). The mean C_max, T_max and t_1/2λz for flunixin following TD administration were 106.4 ng/ml (range, 56.98 to 168.6 ng/ml), 13.57 hr (range, 6.000–34.00 hr) and 24.06 hr (18.63 to 39.5 hr), respectively. The mean bioavailability for TD flunixin was calculated as 25.05%. The mean 80% inhibitory concentration (IC₈₀) of PGE₂ by flunixin meglumine was 0.23 µg/ml (range, 0.01 to 1.38 µg/ml). Poor bioavailability and poor suppression of PGE₂ identified in this study indicate that TD flunixin meglumine administered at 3.3 mg/kg is not recommended for use in alpacas.     

Tilmicosin‐ and florfenicol‐loaded hydrogenated castor oil‐solid lipid nanoparticles to pigs: Combined antibacterial activities and pharmacokinetics

The combined antibacterial effects of tilmicosin (TIL) and florfenicol (FF) against Actinobacillus pleuropneumoniae (APP) (n = 2), Streptococcus suis (S. suis) (n = 2), and Haemophilus parasuis (HPS) (n = 2) were evaluated by chekerboard test and time‐kill assays. The pharmacokinetics (PKs) of TIL‐ and FF‐loaded hydrogenated castor oil (HCO)‐solid lipid nanoparticles (SLN) were performed in healthy pigs. The results indicated that TIL and FF showed synergistic or additive antibacterial activities against APP, S. suis and HPS with the fractional inhibitory concentration (FIC) ranging from 0.375 to 0.75. The time‐kill assays showed that 1/2 minimum inhibitory concentration (MIC) TIL combined with 1/2 MIC FF had a stronger ability to inhibit the growth of APP, S. suis, and HPS than 1 MIC TIL or 1 MIC FF, respectively. After oral administration, plasma TIL and FF concentrations could maintain about 0.1 μg/ml for 192 and 176 hr. The SLN prolonged the last time point with detectable concentrations (T_last), area under the concentration–time curve (AUC_0‐t), elimination half‐life (T_½ke), and mean residence time (MRT) by 3.1, 5.6, 12.7, 3.4‐fold of the active pharmaceutical ingredient (API) of TIL and 11.8, 16.5, 18.1, 12.1‐fold of the API of FF, respectively. This study suggests that the TIL‐FF‐SLN could be a useful oral formulation for the treatment of APP, S. suis, and HPS infection in pigs.