Pharmacokinetics and bioavailability after intramuscular injection of the 5‐HT1A serotonin agonist R‐8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT) in domestic goats (Capra aegagrus hircus)

To determine the bioavailability and pharmacokinetic properties of the serotonin 5‐HT_1A receptor agonist R‐8‐OH‐DPAT in goats, and 0.1 mg kg^?1 R‐8‐OH‐DPAT hydrobromide was administered intramuscularly (i.m.) and intravenously (i.v.) to six goats in a two‐phase cross‐over design experiment. Venous blood samples were collected from the jugular vein 2, 5, 10, 15, 20, 30, 40 and 60 min following treatment and analysed by liquid chromatography tandem mass spectrometry. Bioavailability and pharmacokinetic parameters were determined by a one‐compartment analysis. Mean bioavailability of R‐8‐OH‐DPAT when injected i.m. was 66%. The mean volume of distribution in the central compartment was 1.47 L kg^?1. The mean plasma body clearance was 0.056 L kg^?1 min^?1. All goats injected i.v. and two of six goats injected i.m. showed signs of serotonin toxicity. In conclusion, R‐8‐OH‐DPAT is well absorbed following i.m. injection and the observed pharmacokinetics suggest that administration via dart is feasible. Administration of R‐8‐OH‐DPAT hydrobromide, at a dosage of 0.1 mg kg^?1, resulted in the observation of clinical signs of serotonin toxicity in the goats. It is suggested that dosages for the clinical use of the compound should be lower in order to achieve the desired clinical effect without causing serotonin toxicity.     

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 pharmacodynamics of intramammary cefquinome in lactating goats with and without experimentally induced Staphylococcus aureus mastitis

Values for pharmacokinetic variables are usually obtained in healthy animals, whereas drugs are frequently administered to diseased animals. This study investigated cefquinome pharmacokinetics in healthy goats and goats with experimentally induced mastitis. Five adult lactating goats received 75 mg of cefquinome intramammary infusion using a commercially available product into one udder half in healthy goats and goats with clinical mastitis that was induced by intracisternal infusion of 100 cfu of Staphylococcus aureus ATCC 29213 suspended in 5 ml of sterile culture broth. Cefquinome concentrations were determined in plasma and skimmed milk samples using high‐performance liquid chromatography (HPLC). Pharmacodynamics was investigated using the California Mastitis Test and pH of milk. Experimentally induced mastitis significantly increased the California Mastitis Test score and pH, and decreased the maximal cefquinome concentration and shortened the half‐life in milk when compared to healthy goats. In conclusion, mastitis facilitated the absorption of cefquinome from the mammary gland of lactating goats and induced marked changes in milk pH, emphasizing the importance of performing pharmacokinetic studies of antimicrobial agents in infected animals.     

Pharmacokinetics and pharmacodynamics of intravenous and transdermal flunixin meglumine in meat goats

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 Boer goats. A dose of 2.2 mg/kg was administered intravenously (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 flunixin meglumine for both routes of administration. Mean λ_z‐HL after IV administration was 6.032 hr (range 4.735–9.244 hr) resulting from a mean V_z of 584.1 ml/kg (range, 357.1–1,092 ml/kg) and plasma clearance of 67.11 ml kg^?1 hr^?1 (range, 45.57–82.35 ml kg^?1 hr^?1). The mean C_max, T_max, and λ_z‐HL for flunixin following TD administration was 0.134 μg/ml (range, 0.050–0.188 μg/ml), 11.41 hr (range, 6.00–36.00 hr), and 43.12 hr (15.98–62.49 hr), respectively. The mean bioavailability for TD flunixin was calculated as 24.76%. The mean 80% inhibitory concentration (IC₈₀) of PGE₂ by flunixin meglumine was 0.28 μg/ml (range, 0.08–0.69 μg/ml) and was only achieved with IV formulation of flunixin in this study. The PK results support clinical studies to examine the efficacy of TD flunixin in goats. Determining the systemic effects of flunixin‐mediated PGE₂ suppression in goats is also warranted.     

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.     

Effects of dietary amino acid supplementation on measures of whole‐body and muscle protein metabolism in aged horses

The objective of this study was to examine markers of whole‐body and muscle protein metabolism in aged horses fed a diet typical for North American aged horses, supplemented with amino acids. In a replicated Latin square design, six aged horses (20 ± 1.1 years) were studied while receiving each of three isocaloric, isonitrogenous diets, a control treatment concentrate (CON; 100 mg/kg^?1 BW day^?1 lysine, 84 mg kg^?1 day^?1 threonine, 51 mg kg^?1 day^?1 methionine), LYS/THR (134 mg kg^?1 BW day^?1 lysine, 110 mg kg^?1 BW day^?1 threonine, 52 mg kg^?1 BW day^?1 methionine) and LYS/THR/MET (132 mg kg^?1 BW day^?1 lysine, 112 mg kg^?1 BW day^?1 threonine, 62 mg kg^?1 BW day^?1 methionine). In each 15‐days period, urine and faeces were collected for assessment of nitrogen balance. Blood samples were collected before and after feeding for analysis of plasma urea nitrogen (PUN), glucose, insulin and plasma amino acid concentrations. Skeletal muscle samples were collected for measurement of proteins associated with muscle protein synthesis and degradation, and horses underwent stable isotope infusion procedures for comparison of differences in whole‐body rates of protein synthesis and degradation. There was no effect of treatment on relative abundance of proteins involved in protein synthesis, nitrogen retention or phenylalanine kinetics. PUN concentrations tended to be higher for LYS/THR (p = 0.054) and were higher for LYS/THR/MET (p = 0.0056) than for CON. Atrogin‐1 abundance tended to be higher in the post‐absorptive state for the CON treatment (p = 0.07), indicating that amino acid supplementation resulted in less muscle protein degradation when horses were in the post‐absorptive state. However, lack of differences in nitrogen retention and phenylalanine kinetics indicated that whole‐body protein metabolism was not improved, and higher PUN concentrations in the supplemented diets suggest that the supplemented amino acids may have been catabolized. Amino acid availability was not limiting protein synthesis in the sedentary aged horses in this study when fed the CON diet.     

Pharmacokinetics and bioavailability of danofloxacin in chukar partridge (Alectoris chukar) following intravenous,intramuscular, subcutaneous,and oral administrations

The aim of the present study was to determine the pharmacokinetics (PKs) and bioavailability of danofloxacin in chukar partridge (Alectoris chukar) following intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations at a dose of 10 mg/kg. A total of eight clinically healthy chukar partridges weighing 480 ± 45 g were used for the investigation. The study was performed in a crossover design (2 × 2 × 2 × 2) with a 15‐day washout period between two administrations in four periods. The plasma concentrations of danofloxacin were determined using reversed‐phase high‐performance liquid chromatography. Noncompartmental PK parameters were also estimated. No local or systemic adverse drug effects were observed in any of the chukar partridges. The mean elimination half‐life ranged between 8.18 and 12.08 hr and differed statistically among administration routes. The mean peak plasma concentrations of danofloxacin following IM, SC, and PO administrations were 8.05, 9.58, and 3.39 μg/ml at 0.5, 1, and 4 hr, respectively. Following IM, SC, and PO administrations, the mean bioavailability was 86.33%, 134.40%, and 47.62%, respectively. The mean total clearance and volume of distribution at steady‐state following IV administration were 0.13 L hr^?1 kg^?1 and 0.96 L/kg, respectively. These data, including favorable PKs and the absence of adverse drug effects, suggest that danofloxacin is a useful antibiotic in chukar partridges.     

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.     

Effect of dose on the intravenous pharmacokinetics of tolfenamic acid in goats

The objective of this study was to determine the pharmacokinetics of tolfenamic acid (TA) following intravenous (IV) administration at doses of 2 and 4 mg/kg in goats. In this study, six healthy goats were used. TA was administered intravenously to each goat at 2 and 4 mg/kg doses in a cross-over pharmacokinetic design with a 15-day washout period. Plasma concentrations of TA were analyzed using the high performance liquid chromatography with ultraviolet detector, and pharmacokinetic parameters were assigned by noncompartmental analysis. Following IV administration at dose of 2 mg/kg, area under the concentration–time curve (AUC_0−∞), elimination half-life (t_1/2ʎz), total clearance (Cl_T) and volume of distribution at steady state (V_dss) were 6.64 ± 0.81 hr^*µg/ml, 1.57 ± 0.14 hr, 0.30 ± 0.04 L h^-1 kg^-1 and 0.40 ± 0.05 L/kg, respectively. After the administration of TA at a dose of 4 mg/kg showed prolonged t_1/2ʎz, increased dose-normalized AUC_0-∞, and decreased Cl_T. In goats, TA at 4 mg/kg dose can be administered wider dose intervals compared to the 2 mg/kg dose. However, further studies are needed to determine the effect of different doses on the clinical efficacy of TA in goats.     

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 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.     

Plasma and synovial fluid pharmacokinetics of cefquinome following the administration of multiple doses in horses

The plasma and synovial fluid pharmacokinetics and safety of cefquinome, a 2‐amino‐5‐thiazolyl cephalosporin, were determined after multiple intravenous administrations in sixteen healthy horses. Cefquinome was administered to each horse through a slow i.v. injection over 20 min at 1, 2, 4, and 6 mg/kg (n = 4 horses per dose) every 12 h for 7 days (a total of 13 injections). Serial blood and synovial fluid samples were collected during the 12 h after the administration of the first and last doses and were analyzed by a high‐performance liquid chromatography assay. The data were evaluated using noncompartmental pharmacokinetic analyses. The estimated plasma pharmacokinetic parameters were compared with the hypothetical minimum inhibitory concentration (MIC) values (0.125–2 μg/mL). The plasma and synovial fluid concentrations and area under the concentration–time curves (AUC) of cefquinome showed a dose‐dependent increase. After a first dose of cefquinome, the ranges for the mean plasma half‐life values (2.30–2.41 h), the mean residence time (1.77–2.25 h), the systemic clearance (158–241 mL/h/kg), and the volume of distribution at steady‐state (355–431 mL/kg) were consistent across dose levels and similar to those observed after multiple doses. Cefquinome did not accumulate after multiple doses. Cefquinome penetrated the synovial fluid with AUC_{synovial fluid}/AUC_plasma ratios ranging from 0.57 to 1.37 after first and thirteenth doses, respectively. Cefquinome is well tolerated, with no adverse effects. The percentage of time for which the plasma concentrations were above the MIC was >45% for bacteria, with MIC values of ≤0.25, ≤0.5, and ≤1 μg/mL after the administration of 1, 2, and 4 or 6 mg/kg doses of CFQ at 12‐h intervals, respectively. Further studies are needed to determine the optimal dosage regimes in critically ill patients.     

Pharmacokinetics of levofloxacin after single intravenous,oral and subcutaneous administration to dogs

The pharmacokinetic properties of the fluoroquinolone levofloxacin (LFX) were investigated in six dogs after single intravenous, oral and subcutaneous administration at a dose of 2.5, 5 and 5 mg/kg, respectively. After intravenous administration, distribution was rapid (T_½dist 0.127 ± 0.055 hr) and wide as reflected by the volume of distribution of 1.20 ± 0.13 L/kg. Drug elimination was relatively slow with a total body clearance of 0.11 ± 0.03 L kg^?1 hr^?1 and a T_½ for this process of 7.85 ± 2.30 hr. After oral and subcutaneous administration, absorption half‐life and T_max were 0.35 and 0.80 hr and 1.82 and 2.82 hr, respectively. The bioavailability was significantly higher (p ? 0.05) after subcutaneous than oral administration (79.90 vs. 60.94%). No statistically significant differences were observed between other pharmacokinetic parameters. Considering the AUC_24 hr/MIC and C_max/MIC ratios obtained, it can be concluded that LFX administered intravenously (2.5 mg/kg), subcutaneously (5 mg/kg) or orally (5 mg/kg) is efficacious against Gram‐negative bacteria with MIC values of 0.1 μg/ml. For Gram‐positive bacteria with MIC values of 0.5 μg/kg, only SC and PO administration at a dosage of 5 mg/kg showed to be efficacious. MIC‐based PK/PD analysis by Monte Carlo simulation indicates that the proposed dose regimens of LFX, 5 and 7.5 mg/kg/24 hr by SC route and 10 mg/kg/24 hr by oral route, in dogs may be adequate to recommend as an empirical therapy against S. aureus strains with MIC ≤ 0.5 μg/ml and E. coli strains with MIC values ≤0.125 μg/ml.     

Pharmacokinetics of the novel COX‐2 selective inhibitor vitacoxib in cats: The effects of feeding and dose

The purpose of this study was to determine the pharmacokinetics and dose‐scaling model of vitacoxib in either fed or fasted cats following either oral or intravenous administration. The concentration of the drug was quantified by UPLC‐MS/MS on plasma samples. Relevant parameters were described using noncompartmental analysis (WinNonlin 6.4 software). Vitacoxib is relatively slowly absorbed and eliminated after oral administration (2 mg/kg body weight), with a T_max of approximately 4.7 hr. The feeding state of the cat was a statistically significant covariate for both area under the concentration versus time curve (AUC) and mean absorption time (MAT_fed). The absolute bioavailability (F) of vitacoxib (2 mg/kg body weight) after oral administration (fed) was 72.5%, which is higher than that in fasted cats (F = 50.6%). Following intravenous administration (2 mg/kg body weight), Vd (ml/kg) was 1,264.34 ± 343.63 ml/kg and Cl (ml kg^?1 hr^?1) was 95.22 ± 23.53 ml kg^?1 hr^?1. Plasma concentrations scaled linearly with dose, with C_max (ng/ml) of 352.30 ± 63.42, 750.26 ± 435.54, and 936.97 ± 231.27 ng/ml after doses of 1, 2, and 4 mg/kg body weight, respectively. No significant undesirable behavioral effects were noted throughout the duration of the study.     

In vivo activity of cefquinome against Riemerella anatipestifer using the pericarditis model in the duck

Cefquinome is a fourth‐generation cephalosporin with broad‐spectrum antibacterial activity, including activity against enteric gram‐negative bacilli such as Riemerella anatipestifer. The pericarditis model was used to examine the pharmacodynamic characteristics of cefquinome against R. anatipestifer. Serum levels of cefquinome following the administration of different doses were determined by LC‐MS/MS. Ducks with ca. 10⁶ CFU/mL at the initiation of therapy were treated with cefquinome at doses that ranged from 0.0156 to 2 mg/kg of body weight/day (in 3, 6, 12, or 24 divided doses) for 24 h. The percentage of a 24‐h dosing interval that the unbound serum cefquinome concentrations exceeded the MIC (fT > MIC) were the pharmacokinetic (PK)–pharmacodynamic (PD) parameter that best correlated with efficacy (R² 86.3% for R. anatipestifer, compared with 58.9% for the area under the concentration–time curve/MIC and 10.6% for peak/MIC). A sigmoid E_max model was used to estimate the magnitudes of the %fT > MIC associated with net bacterial stasis, a 1‐log₁₀ CFU reduction from baseline, and a 2‐log₁₀ CFU reduction from baseline; the corresponding values were (22.5 ± 1.3) %, (35.2 ± 4.5) %, and (42.4 ± 2.7) %. These data showed that treatment with cefquinome results in marked antibacterial effects in qvivo against R. anatipestifer and that the host's immunity may also play a key role in the anti‐infective therapy process.     

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.     

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.     

Pharmacokinetics of sodium baicalin following intravenous and intramuscular administration to piglets

The purpose of this study was to determine the pharmacokinetics of baicalin after intravenous and intramuscular administration of sodium baicalin at 50 mg/kg to piglets. Plasma baicalin levels were determined by high‐performance liquid chromatography. The plasma concentration–time data of baicalin for both administration routes were best described by two‐compartmental open model. The area under the plasma concentration–time curve and the elimination half‐lives were 77.47 ± 6.14 µg/ml × h and 1.73 ± 0.16 hr for intravenous and 64.85 ± 5.67 µg/ml × h and 2.42 ± 0.15 hr for intramuscular administration, respectively. The apparent volume of distribution and body clearance were 1.63 ± 0.23 L/kg and 2.74 ± 0.30 L h^?1 kg^?1 for intravenous and 0.51 ± 0.10 L/kg and 0.78 ± 0.08 L h^?1 kg^?1 for intramuscular routes, respectively. An intramuscular injection of sodium baicalin in piglets resulted in rapid and complete absorption, with a mean maximal plasma concentration of 77.28 ± 7.40 µg/ml at 0.17 hr and a high absolute bioavailability of 83.73 ± 5.53%.     

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.     

Pharmacokinetic study of oral amitriptyline in horses

The purpose of this study was to evaluate the pharmacokinetics of oral amitriptyline in horses. Oral amitriptyline (1 mg/kg) was administered to six horses. Blood samples were collected from jugular and lateral thoracic vein at predetermined times from 0 to 24 hr after administration. Plasma concentrations were determined by high-performance liquid chromatography and analyzed using noncompartmental methods. Pharmacodynamic parameters including heart rate, respiration rate, and intestinal motility were evaluated, and electrocardiographic examinations were performed in all subjects. The mean maximum plasma concentration (C_max) of amitriptyline was 30.7 ng/ml, time to maximum plasma concentration (T_max) 1–2 hr, elimination half-life (t_1/2) 17.2 hr, area under plasma concentration–time curve (AUC) 487.4 ng ml⁻¹ hr⁻¹, apparent clearance (Cl/F) 2.6 L hr⁻¹ kg⁻¹, and apparent volume of distribution (Vd/F) 60.1 L/kg. Jugular vein sampling overestimated the amount of amitriptyline absorbed and should not be used to study uptake following oral administration. Heart rate and intestinal motility showed significant variation (p < .05). Electrocardiography did not provide conclusive results. Further studies are required to discern if multiple dose treatment would take the drug to steady state as expected, consequently increasing plasma concentrations.