Pharmacokinetics of levamisole in the red‐eared slider turtles (Trachemys scripta elegans)

The pharmacokinetics and bioavailability of levamisole were determined in red‐eared slider turtles after single intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. Nine turtles received levamisole (10 mg/kg) by each route in a three‐way crossover design with a washout period of 30 days. Blood samples were collected at time 0 (pretreatment), and at 0.25, 0.5, 1, 1.5, 3, 6, 9, 12, 18, 24, 36, and 48 hr after drug administration. Plasma levamisole concentrations were determined by a high‐performance liquid chromatography assay. Data were analyzed by noncompartmental methods. The mean elimination half‐life was 5.00, 7.88, and 9.43 hr for IV, IM, and SC routes, respectively. The total clearance and volume of distribution at steady state for the IV route were 0.14 L hr^?1 kg^?1 and 0.81 L/kg, respectively. For the IM and SC routes, the peak plasma concentration was 9.63 and 10.51 μg/ml, respectively, with 0.5 hr of T_max. The bioavailability was 93.03 and 115.25% for the IM and SC routes, respectively. The IM and SC route of levamisole, which showed the high bioavailability and long t_1/2?z, can be recommended as an effective way for treating nematodes in turtles.     

Pharmacokinetics of cefquinome in red‐eared slider turtles (Trachemys scripta elegans) after single intravenous and intramuscular injections

The purpose of this study was to evaluate the pharmacokinetics of cefquinome (CFQ ) following single intravenous (IV ) or intramuscular (IM ) injections of 2 mg/kg body weight in red‐eared slider turtles. Plasma concentrations of CFQ were determined by high‐performance liquid chromatography and analyzed using noncompartmental methods. The pharmacokinetic parameters following IV injection were as follows: elimination half‐life (t _1/2λz) 21.73 ± 4.95 hr, volume of distribution at steady‐state (V _dss) 0.37 ± 0.11 L/kg, area under the plasma concentration–time curve (AUC _0–∞) 163 ± 32 μg hr^?1 ml^?1, and total body clearance (Cl_T) 12.66 ± 2.51 ml hr^?1 kg^?1. The pharmacokinetic parameters after IM injection were as follows: peak plasma concentration (C _max) 3.94 ± 0.84 μg/ml, time to peak concentration (T _max) 3 hr, t _1/2λz 26.90 ± 4.33 hr, and AUC _0–∞ 145 ± 48 μg hr^?1 ml^?1. The bioavailability after IM injection was 88%. Data suggest that CFQ has a favorable pharmacokinetic profile with a long half‐life and a high bioavailability in red‐eared slider turtles. Further studies are needed to establish a multiple dosage regimen and evaluate clinical efficacy.     

Pharmacokinetics and bioavailability of cefquinome and ceftriaxone in premature calves

The aim of this study was to evaluate the pharmacokinetics and bioavailability of cefquinome (CFQ) and ceftriaxone (CTX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. Using a parallel design, 24 premature calves were randomly divided into the two antibiotic groups. Each of the six animals in the first group received CFQ (2 mg/kg) through IV or IM administration. The second group received CTX (20 mg/kg) via the same administration route. Plasma concentrations of the drugs were analyzed by high‐performance liquid chromatography and noncompartmental methods. Mean pharmacokinetic parameters of CFQ and CTX following IV administration were as follows: elimination half‐life (t_1/2λz) 1.85 and 3.31 hr, area under the plasma concentration–time curve (AUC_0–∞) 15.74 and 174 hr * μg/ml, volume of distribution at steady‐state 0.37 and 0.45 L/kg, and total body clearance 0.13 and 0.12 L hr^?1 kg^?1, respectively. Mean pharmacokinetic parameters of CFQ and CTX after IM injection were as follows: peak concentration 4.56 and 25.04 μg/ml, time to reach peak concentration 1 and 1.5 hr, t_1/2λz 4.74 and 3.62 hr, and AUC_0–∞ 22.75 and 147 hr * μg/ml, respectively. The bioavailability of CFQ and CTX after IM injection was 141% and 79%, respectively. IM administration of CFQ (2 mg/kg) and CTX (20 mg/kg) can be recommended at 12‐hr interval for treating infections caused by susceptible bacteria, with minimum inhibitory concentration values of ≤0.5 and ≤4 μg/ml, respectively, in premature calves. However, further research is indicated to assess the pharmacokinetic parameters following multiple doses of the drug in premature calves.     

Pharmacokinetics of enrofloxacin and danofloxacin in premature calves

The aim of this study was to determine the pharmacokinetics/pharmacodynamics of enrofloxacin (ENR) and danofloxacin (DNX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. The study was performed on twenty‐four calves that were determined to be premature by anamnesis and general clinical examination. Premature calves were randomly divided into four groups (six premature calves/group) according to a parallel pharmacokinetic (PK) design as follows: ENR‐IV (10 mg/kg, IV), ENR‐IM (10 mg/kg, IM), DNX‐IV (8 mg/kg, IV), and DNX‐IM (8 mg/kg, IM). Plasma samples were collected for the determination of tested drugs by high‐pressure liquid chromatography with UV detector and analyzed by noncompartmental methods. Mean PK parameters of ENR and DNX following IV administration were as follows: elimination half‐life (t_1/2λz) 11.16 and 17.47 hr, area under the plasma concentration–time curve (AUC_0‐48) 139.75 and 38.90 hr*µg/ml, and volume of distribution at steady‐state 1.06 and 4.45 L/kg, respectively. Total body clearance of ENR and DNX was 0.07 and 0.18 L hr^?1 kg^?1, respectively. The PK parameters of ENR and DNX following IM injection were t_1/2λz 21.10 and 28.41 hr, AUC_0‐48 164.34 and 48.32 hr*µg/ml, respectively. The bioavailability (F) of ENR and DNX was determined to be 118% and 124%, respectively. The mean AUC_0‐48CPR/AUC_0‐48ENR ratio was 0.20 and 0.16 after IV and IM administration, respectively, in premature calves. The results showed that ENR (10 mg/kg) and DNX (8 mg/kg) following IV and IM administration produced sufficient plasma concentration for AUC_0‐24/minimum inhibitory concentration (MIC) and maximum concentration (C_max)/MIC ratios for susceptible bacteria, with the MIC₉₀ of 0.5 and 0.03 μg/ml, respectively. These findings may be helpful in planning the dosage regimen for ENR and DNX, but there is a need for further study in naturally infected premature calves.     

Pharmacokinetics of a single intramuscular injection of cefquinome in buffalo calves

The objective of this study was to investigate the pharmacokinetics of cefquinome following single intramuscular (IM) administration in six healthy male buffalo calves. Cefquinome was administered intramuscularly (2 mg/kg bodyweight) and blood samples were collected prior to drug administration and up to 24 hr after injection. No adverse effects or changes were observed after the IM injection of cefquinome. Plasma concentrations of cefquinome were determined by high‐performance liquid chromatography. The disposition of plasma cefquinome is characterized by a mono‐compartmental open model. The pharmacokinetic parameters after IM administration (mean ± SE) were C_max 6.93 ± 0.58 μg/ml, T_max 0.5 hr, t_½kα 0.16 ± 0.05 hr, t_½β 3.73 ± 0.10 hr, and AUC 28.40 ± 1.30 μg hr/ml after IM administration. A dosage regimen of 2 mg/kg bodyweight at 24‐hr interval following IM injection of cefquinome would maintain the plasma levels required to be effective against the bacterial pathogens with MIC values ≤0.39 μg/ml. The suggested dosage regimen of cefquinome has to be validated in the disease models before recommending for clinical use in buffalo calves.     

Differential pharmacokinetics and pharmacokinetic/pharmacodynamic modelling of robenacoxib and ketoprofen in a feline model of inflammation

Robenacoxib and ketoprofen are acidic nonsteroidal anti‐inflammatory drugs (NSAIDs). Both are licensed for once daily administration in the cat, despite having short blood half‐lives. This study reports the pharmacokinetic/pharmacodynamic (PK/PD) modelling of each drug in a feline model of inflammation. Eight cats were enrolled in a randomized, controlled, three‐period cross‐over study. In each period, sterile inflammation was induced by the injection of carrageenan into a subcutaneously implanted tissue cage, immediately before the subcutaneous injection of robenacoxib (2 mg/kg), ketoprofen (2 mg/kg) or placebo. Blood samples were taken for the determination of drug and serum thromboxane (Tx)B₂ concentrations (measuring COX‐1 activity). Tissue cage exudate samples were obtained for drug and prostaglandin (PG)E₂ concentrations (measuring COX‐2 activity). Individual animal pharmacokinetic and pharmacodynamic parameters for COX‐1 and COX‐2 inhibition were generated by PK/PD modelling. S(+) ketoprofen clearance scaled by bioavailability (CL/F) was 0.114 L/kg/h (elimination half‐life = 1.62 h). For robenacoxib, blood CL/F was 0.684 L/kg/h (elimination half‐life = 1.13 h). Exudate elimination half‐lives were 25.9 and 41.5 h for S(+) ketoprofen and robenacoxib, respectively. Both drugs reduced exudate PGE₂ concentration significantly between 6 and 36 h. Ketoprofen significantly suppressed (>97%) serum TxB₂ between 4 min and 24 h, whereas suppression was mild and transient with robenacoxib. In vivoIC₅₀COX‐1/IC₅₀COX‐2 ratios were 66.9:1 for robenacoxib and 1:107 for S(+) ketoprofen. The carboxylic acid nature of both drugs may contribute to the prolonged COX‐2 inhibition in exudate, despite short half‐lives in blood.     

Pharmacokinetics of cefquinome in healthy and Pasteurella multocida‐infected rabbits

The pharmacokinetics of cefquinome were studied in healthy and Pasteurella multocida‐infected rabbits after a single intramuscular (IM) injection at 2 mg/kg of its sulfate salt. Twelve female New Zealand white rabbits (2.0–2.5 kg) were used; six of them served as controls, and the other six had been infected with P. multocida; the experiments were conducted 1–2 days after nasal inoculation of P. multocida when rabbits showed the signs of respiratory infection. Plasma concentrations of cefquinome were determined using high‐performance liquid chromatography. The values of elimination half‐life, area under the curve, area under the first moment curve, and mean residence time were significantly lower in infected rabbits (0.48 hr, 4.54 hr*μg/ml, 3.63 hr* hr*μg/ml and 0.8 hr, respectively) than healthy rabbits (0.72 hr, 9.11 hr*μg/ml, 9.85 hr* hr*μg/ml and 1.1 hr, respectively), whereas total body clearance was significantly higher in infected than healthy rabbits. Therefore, P. multocida infection caused significant changes in some of the pharmacokinetic parameters of cefquinome in rabbits. These pharmacokinetic changes may affect dose regimen when used in P. multocida‐infected rabbits.     

Pharmacokinetics and pharmacodynamics of alfaxalone after a single intramuscular or intravascular injection in mallard ducks (Anas platyrhynchos)

Pharmacokinetics and pharmacodynamics of alfaxalone was performed in mallard ducks (Anas platyrhynchos) after single bolus injections of 10 mg/kg administered intramuscularly (IM; n = 10) or intravenously (IV; n = 10), in a randomized cross‐over design with a washout period between doses. Mean (±SD) C_max following IM injection was 1.6 (±0.8) µg/ml with T_max at 15.0 (±10.5) min. Area under the curve (AUC) was 84.66 and 104.58 min*mg/ml following IV and IM administration, respectively. Volume of distribution (V_D) after IV dose was 3.0 L/kg. The mean plasma clearance after 10 mg/kg IV was 139.5 (±67.9) ml min^?1 kg^?1. Elimination half‐lives (mean [±SD]) were 15.0 and 16.1 (±3.0) min following IV and IM administration, respectively. Mean bioavailability at 10 mg/kg IM was 108.6%. None of the ducks achieved a sufficient anesthetic depth for invasive procedures, such as surgery, to be performed. Heart and respiratory rates measured after administration remained stable, but many ducks were hyperexcitable during recovery. Based on sedation levels and duration, alfaxalone administered at dosages of 10 mg/kg IV or IM in mallard ducks does not induce clinically acceptable anesthesia.     

Population pharmacokinetics of ceftazidime after a single intramuscular injection in wild turtles

Ceftazidime, a third‐generation cephalosporin, is important for treating opportunistic bacterial infections in turtles. Antibacterial dosage regimens are not well established for wild turtles and are often extrapolated from other reptiles or mammals. This investigation used a population pharmacokinetic approach to study ceftazidime in wild turtles presented for rehabilitation. Ceftazidime was administered to 24 wild turtles presented to the Turtle Rescue Team at North Carolina State University. A sparse blood sampling protocol was used to collect samples from 0 to 120 hr with three samples per individual after injection. Plasma samples were analyzed by high‐pressure liquid chromatography (HPLC). A nonlinear mixed‐effects model (NLME) was fitted to the data to determine typical values for population parameters. We identified a long half‐life (T½) of approximately 35 hr and volume of distribution (V_SS) of 0.26 L/kg. We concluded that this long T½ will allow for a dose of 20 mg/kg injected IM to maintain concentrations above the MIC of most wild‐type bacteria for 5 days. Because of long intervals between injections, stability of stored formulations was measured and showed that 90% strength was maintained for 120 hr when stored in the refrigerator and for 25 days when stored in the freezer.     

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.     

Resistant cutoff values and optimal scheme establishments for florfenicol against Escherichia coli with PK‐PD modeling analysis in pigs

Florfenicol, a structural analog of thiamphenicol, has broad‐spectrum antibacterial activity against gram‐negative and gram‐positive bacteria. This study was conducted to investigate the epidemiological, pharmacokinetic–pharmacodynamic cutoff, and the optimal scheme of florfenicol against Escherichia coli (E. coli) with PK‐PD integrated model in the target infectious tissue. 220 E. coli strains were selected to detect the susceptibility to florfenicol, and a virulent strain P190, whose minimum inhibitory concentration (MIC) was similar to the MIC₅₀ (8 μg/ml), was analyzed for PD study in LB and ileum fluid. The MIC of P190 in the ileum fluid was 0.25 times lower than LB. The ratios of MBC/MIC were four both in the ileum and LB. The characteristics of time‐killing curves also coincided with the MBC determination. The recommended dosages (30 mg/kg·body weight) were orally administrated in healthy pigs, and both plasma and ileum fluid were collected for PK study. The main pharmacokinetics (PK) parameters including AUC_24 hr, AUC_0–∞, T_max, T_1/2, C_max, CL_b, and K_e were 49.83, 52.33 μg*h/ml, 1.32, 10.58 hr, 9.12 μg/ml, 0.50 L/hr*kg, 0.24 hr^?1 and 134.45, 138.71 μg*hr/ml, 2.05, 13.01 hr, 16.57 μg/ml, 0.18 L/hr*kg, 0.14 hr^?1 in the serum and ileum fluid, respectively. The optimum doses for bacteriostatic, bactericidal, and elimination activities were 29.81, 34.88, and 36.52 mg/kg for 50% target and 33.95, 39.79, and 42.55 mg/kg for 90% target, respectively. The final sensitive breakpoint was defined as 16 μg/ml. The current data presented provide the optimal regimens (39.79 mg/kg) and susceptible breakpoint (16 μg/ml) for clinical use, but these predicted data should be validated in the clinical practice.     

Pharmacokinetics of levosulpiride after single‐dose administration in goats (Capra hircus) by different routes of administration

Levosulpiride (LSP) is the l‐enantiomer of sulpiride, and LSP recently replacing sulpiride in several EU countries. Several studies about LSP in humans are present in the literature, but neither pharmacodynamic nor pharmacokinetic data of LSP is present for veterinary species. The aim of this study was to assess the pharmacokinetic profile of LSP after intravenous (IV), intramuscular (IM), and oral (PO) administration in goats. Animals (n = 6) were treated with 50 mg LSP by IV, IM, and PO routes according to a randomized cross‐over design (3 × 3 Latin‐square). Blood samples were collected prior and up to 24 hr after LSP administration and quantified using a validated HPLC method with fluorescence detection. IV and IM administration gave similar concentration versus time curve profiles. The IM mean bioavailability was 66.97%. After PO administration, the drug plasma concentrations were detectable only in the time range 1.5–4 hr, and the bioavailability (4.73%) was low. When the AUC was related to the administered dose in mg/kg, there was a good correlation in the IV and IM groups, but very low correlation for the PO route. In conclusion, the IM and IV administrations result in very similar plasma concentrations. Oral dosing of LSP in goats is probably not viable as its oral bioavailability was very low.     

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 of ceftriaxone in Green sea turtles (Chelonia mydas) following intravenous and intramuscular administration at two dosages

Green sea turtles are widely distributed in tropical and subtropical waters. Adult green sea turtles face many threats, primarily from humans, including injuries from boat propellers, being caught in fishing nets, pollution, poaching, and infectious diseases. To the best of our knowledge, limited pharmacokinetic information to establish suitable therapeutic plans is available for green sea turtles. Therefore, the present study aimed to describe the pharmacokinetic characteristics of ceftriaxone (CEF) in green sea turtles, Chelonia mydas, following single intravenous and intramuscular administrations at two dosages of 10 and 25 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 96 hr. The plasma concentrations of CEF were measured by liquid chromatography tandem mass spectrometry. The concentrations of CEF in the plasma were quantified up to 24 and 48 hr after i.v. and i.m. administrations at dosages of 10 and 25 mg/kg b.w., respectively. The C_max values of CEF were 15.43 ± 3.71 μg/ml and 43.48 ± 4.29 μg/ml at dosages of 10 and 25 mg/kg, respectively. The AUC_last values increased in a dose‐dependent fashion. The half‐life values were 2.89 ± 0.41 hr and 5.96 ± 0.26 hr at dosages of 10 and 25 mg/kg b.w, respectively. The absolute i.m. bioavailability was 67% and 108%, and the binding percentage of CEF to plasma protein was ranged from 20% to 29% with an average of 24.6%. Based on the pharmacokinetic data, susceptibility break‐point and PK‐PD index (T > MIC, 0.2 μg/ml), i.m. administration of CEF at a dosage of 10 mg/kg b.w. might be appropriate for initiating treatment of susceptible bacterial infections in green sea turtles.     

Evaluation of plasma concentration after intravenous and intramuscular penicillin administration over 24 hr in healthy adult horses

Penicillin is administered intravenously (IV) or intramuscularly (IM) to horses for the prevention and treatment of infections, and both routes have disadvantages. To minimize these shortcomings, a 24‐hr hybrid administration protocol (HPP) was developed. Our objective was to determine penicillin plasma concentrations in horses administered via HPP. Venous blood was collected from seven healthy horses administered IV potassium penicillin G at 0 and 6 hr and IM procaine penicillin G at 12 hr. Blood was collected at 2‐hr intervals from 0 to 20 hr and at 24 hr. Plasma penicillin concentrations were measured using liquid chromatography and mass spectrometry. Penicillin susceptibility from equine isolates was examined to determine pharmacodynamic targets. The MIC₉₀ of penicillin for 264 isolates of Streptococcus sp. was ≤0.06 μg/ml. For the 24‐hr dosing interval, the mean plasma penicillin concentration was >0.07 μg/ml. Five horses (72%) exceeded 0.06 μg/ml for 98% of the dosing interval, and two horses exceeded this value for 52%–65% of the dosing interval. The HPP achieved mean plasma penicillin concentrations in healthy adult horses above 0.07 μg/ml for a 24‐hr dosing interval. However, individual variations in plasma concentrations were apparent and deserve future clinical study.     

Pharmacokinetics of injectable marbofloxacin after intravenous and intramuscular administration in red-eared sliders (Trachemys scripta elegans)

Fluoroquinolone antibacterial drugs are currently used in reptilian medicine because of their broad spectrum of activity including the most frequent pathogens of these species. The disposition kinetics of marbofloxacin (MBX) at a single dose of 2 mg/kg were determined in healthy red-eared sliders after intravenous (IV) and intramuscular (IM) administration. The influence of renal portal system on the bioavailability of the drug was investigated by using forelimb and hindlimb as IM injection sites. Apparent volume of distribution at steady-state (V_ss) and systemic clearance (Cl) of marbofloxacin after IV administration were estimated to be 48.21 ± 5.42 ml/kg and 23.38 ± 2.90 ml/hr·kg, respectively. The absolute bioavailabilities after IM route were 45.96% (forelimb) and 52.09% (hindlimb). The lack of statistically significant differences in most of the pharmacokinetic parameters after the two IM injection sites suggests a negligible influence of renal portal system in clinical use of MBX, although the C_max after IM_fore administration is advantageous, having into account the concentration-dependent action of this antibiotic. The absence of visible adverse reactions in the animals and the advantageous pharmacokinetic properties suggest the possibility of its safe and effective clinical use in red-eared sliders.     

Pharmacokinetics and bioavailability of carbetocin after intravenous and intramuscular administration in cows and gilts

The pharmacokinetics of carbetocin, which is used to control postpartum hemorrhage after giving birth, was studied in cows and gilts after a single intravenous (IV) or intramuscular (IM) injection. Blood samples from animals were assessed by oxytocin radioimmunoassay, and then the pharmacokinetic parameters were calculated using a noncompartmental model. For gilts, there was no significant difference between half-life (T_1/2λZ), mean residue time (MRT), and maximum concentration (C_max) between IM and IV administration. Conversely, the time to reach the C_max (T_max) and MRT were higher following administration of 350 μg/animal in cows via the IM administration compared with IV. The longest T_1/2λZ was 0.85 hr, indicating carbetocin was absorbed and eliminated rapidly in both animal species after administration. The T_max was similar between cows and gilts following IM administration. Moreover, the C_max after IM injection was about half that of IV administration in both animals. The bioavailability was more than 80% in cows, suggesting administration via the IM route is efficient. This is in agreement with the longer T_1/2λZ in cows after IM administration. However, the IV route is recommended for gilts due to a lower bioavailability (35%) and shorter T_1/2λZ after IM administration compared with IV.     

Pharmacokinetics of midazolam and its major metabolite 1‐hydroxymidazolam in the ball python (Python regius) after intracardiac and intramuscular administrations

Midazolam is a benzodiazepine with sedative, muscle relaxant, anxiolytic, and anticonvulsant effects. Twelve ball pythons (Python regius) were used in a parallel study evaluating the pharmacokinetics of 1 mg/kg midazolam following a single intracardiac (IC) or intramuscular (IM) administration. Blood was collected from a central venous catheter placed 7 days prior, or by cardiocentesis, at 15 time points starting just prior to and up to 72 hr after drug administration. Plasma concentrations of midazolam and 1‐hydroxymidazolam were determined by the use of high‐performance liquid chromatography tandem‐mass spectrometry and pharmacokinetic parameters were estimated using noncompartmental analysis. The mean ± SD terminal half‐lives of IC and IM midazolam were 12.04 ± 3.25 hr and 16.54 ± 7.10 hr, respectively. The area under the concentration‐time curve extrapolated to infinity, clearance, and apparent volume of distribution in steady‐state of IC midazolam were 19,112.3 ± 3,095.9 ng*hr/ml, 0.053 ± 0.008 L hr^?1 kg^?1, and 0.865 ± 0.289 L/kg, respectively. The bioavailability of IM midazolam was estimated at 89%. Maximum plasma concentrations following an IM administration were reached 2.33 ± 0.98 hr and 24.00 ± 14.12 hr postinjection for midazolam and 1‐hydroxymidazolam, respectively, and 22.33 ± 20.26 hr postinjection for 1‐hydroxymidazolam following IC administration.     

Pharmacokinetics of nebulized and subcutaneously implanted terbinafine in cottonmouths (Agkistrodon piscivorus)

Ophidiomyces ophiodiicola, the causative agent of snake fungal disease, is proposed as a serious threat to the conservation of several snake populations. The objective of this study was to determine the pharmacokinetic parameters of terbinafine administered through nebulization and a sustained subcutaneous implant as potential treatments of Ophidiomyces in reptiles. Seven adult cottonmouths (Agkistrodon piscivorus) were used in single‐dose trials. Each snake was nebulized with terbinafine (2 mg/ml) for 30 min and had blood collected before nebulization and up to 12 hr after nebulization. Following a 5‐month washout, the same snakes were administered a subcutaneous implant containing 24.5 mg terbinafine; blood was collected at baseline, 1 day postimplant placement, and then once weekly for 9 weeks. Plasma for both studies was analyzed by high‐performance liquid chromatography. The mean plasma concentrations of nebulized terbinafine peaked between 0.5 and 4 hr. The subcutaneously implanted terbinafine reached therapeutic concentrations on day 1 and maintained therapeutic for over 6 weeks. These methods and doses are recommended as potential treatment options for snake fungal disease in reptiles.     

Pharmacokinetics of ketorolac in wild Eastern box turtles (Terrapene carolina carolina) after single intramuscular administration

Ketorolac is a nonsteroidal anti‐inflammatory drug that possesses potent analgesic activity comparable to morphine. The opioid shortage in the United States has led to an unreliable supply of opioids for use in rehabilitation facilities, thus underscoring the need for research on the safe and effective use of nonopioid alternatives. The goal of this study was to determine the pharmacokinetics of ketorolac after a single 0.25 mg/kg intramuscular injection administered to injured Eastern box turtles (Terrapene carolina carolina). A sparse blood sampling protocol was used to collect samples from 32 wild turtles that presented to the Turtle Rescue Team at North Carolina State University for traumatic injuries. Blood was collected from 0 to 24 hr after injection and analyzed via high‐pressure liquid chromatography (HPLC). A nonlinear mixed‐effects (NLME) model was fitted to the data to obtain typical values for population parameters. Using this approach, we identified a long half‐life (T_1/2) of 9.78 hr and a volume of distribution (V_ss) of 0.26 L/kg. We have concluded that this long T_1/2 for a dose of 0.25 mg/kg ketorolac‐injected IM provides plasma levels above a previously published target level for 24‐hour analgesia to allow for once daily dosing.