Pharmacokinetic profiles of the active metamizole metabolites after four different routes of administration in healthy dogs

Metamizole (MT), an analgesic and antipyretic drug, is rapidly hydrolyzed to the active primary metabolite 4‐methylaminoantipyrine (MAA) and relatively active secondary metabolite 4‐aminoantipyrine (AA). The aim of this study was to assess the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.), intramuscular (i.m.), oral (p.o.), and rectal (RC) routes in dogs. Six dogs were randomly allocated to an open, single‐dose, four‐treatment, four‐phase, unpaired, crossover study design. Blood was collected at predetermined times within 24 hr, and plasma was analyzed by a validated HPLC‐UV method. Plasma concentrations of MAA and AA after i.v., i.m., p.o., and RC administrations of MT were detectable from 5 (i.v. and i.m.) or 30 (p.o. and RC) min to 24 hr in all dogs. The highest concentrations of MAA were found in the i.v., then i.m., p.o., and RC groups. Plasma concentrations of AA were similar for i.v., i.m., and RC, and the concentrations were approximately double those in the PO groups. The AUC_EV/IV ratio for MAA was 0.75 ± 0.11, 0.59 ± 0.08, and 0.32 ± 0.05, for i.m., p.o., and RC, respectively. The AUC_EV/IV ratio for AA was 1.21 ± 0.33, 2.17 ± 0.62, and 1.08 ± 0.19, for i.m., p.o., and RC, respectively. Although further studies are needed, rectal administration seems to be the least suitable route of administration for MT in the dog.     

Pharmacokinetics of tigecycline in turkeys following different routes of administration

The aim of this research had been to determine the pharmacokinetics of tigecycline (TIG) in turkey after intravenous (i.v.), intramuscular (i.m.), subcutaneous (s.c.), and oral (p.o.) administration at a dose of 10 mg/kg. TIG concentrations in plasma were determined using high‐performance liquid chromatography with tandem mass spectrometry. Mean concentrations of TIG in turkey plasma in the i.v. group were significantly higher than concentrations of this drug obtained after using the other administration routes. No significant differences were demonstrated in respect to the concentrations achieved after i.m. and s.c. administration. The bioavailability of TIG after i.m., s.c., and p.o. administration was 32.59 ± 5.99%, 34.91 ± 9.62%, and 0.97 ± 0.57%, respectively. Values of half‐life in the elimination phase were 23.49 ± 6.51 hr, 25.42 ± 4.42 hr, and 26.62 ± 5.19 hr in i.v., i.m., and s.c. groups, respectively, values of mean residence time were 7.92 ± 1.41 hr, 19.62 ± 2.82 hr, and 17.55 ± 2.59 hr in i.v., i.m., and s.c. groups, respectively, whereas the volume of distribution was 14.85 ± 5.71 L/kg, 14.68 ± 2.56 L/kg, and 15.37 ± 3.00 L/kg in i.v., i.m., and s.c. groups, respectively. Because TIG is not absorbed from the gastrointestinal tract in turkeys to a clinically significant degree, this drug given p.o. could find application in commercial turkey farms only to treat gastrointestinal tract infections.     

Pharmacokinetic profiles of metamizole (dipyrone) active metabolites in goats and its residues in milk

Metamizole (dipyrone, MET) is a nonopioid analgesic drug commonly used in human and veterinary medicine. The aim of this study was to assess two major active metabolites of MET, 4‐methylaminoantipyrin (MAA) and 4‐aminoantipyrin (AA), in goat plasma after intravenous (IV) and intramuscular (IM) administration. In addition, metabolite concentration in milk was monitored after IM injection. Six healthy female goats received MET at a dose of 25 mg/kg by IV and IM routes in a crossover design study. The blood and milk samples were analyzed using HPLC coupled with ultraviolet detector and the plasma vs concentration curves analyzed by a noncompartmental model. In the goat, the MET rapidly converted into MAA and the mean maximum concentration was 183.97 μg/ml (at 0.08 hr) and 51.94 μg/ml (at 0.70 hr) after IV and IM administration, respectively. The area under the curve and mean residual time values were higher in the IM than the IV administered goats. The average concentration of AA was lower than MAA in both groups. Over 1 μg/ml of MAA was found in the milk (at 48 hr) after MET IM administration. In conclusion, IM is considered to be a better administration route in terms of its complete absorption with long persistence in the plasma. However, this therapeutic option should be considered in light of the likelihood of there being milk residue.     

Pharmacokinetic profiles of the active metamizole metabolites in healthy horses

Metamizole (MT) is an analgesic and antipyretic drug labelled for use in humans, horses, cattle, swine and dogs. MT is rapidly hydrolysed to the active primary metabolite 4‐methylaminoantipyrine (MAA). MAA is formed in much larger amounts compared with other minor metabolites. Among the other secondary metabolites, 4‐aminoantipyrine (AA) is also relatively active. The aim of this research was to evaluate the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.) and intramuscular (i.m.) routes in healthy horses. Six horses were randomly allocated to two equally sized treatment groups according to a 2 × 2 crossover study design. Blood was collected at predetermined times within 24 h, and plasma was analysed by a validated HPLC‐UV method. No behavioural changes or alterations in health parameters were observed in the i.v. or i.m. groups of animals during or after (up to 7 days) drug administration. Plasma concentrations of MAA after i.v. and i.m. administrations of MT were detectable from 5 min to 10 h in all the horses. Plasma concentrations of AA were detectable in the same range of time, but in smaller amounts. Maximum concentration (C_max), time to maximum concentration (T_max) and AUMC_0‐last of MAA were statistically different between the i.v. and i.m. groups. The AUC_IM/AUC_IV ratio of MAA was 1.06. In contrast, AUC_0‐last of AA was statistically different between the groups (P < 0.05) with an AUC_IM/AUC_IV ratio of 0.54. This study suggested that the differences in the MAA and AA plasma concentrations found after i.m. and i.v. administrations of MT might have minor consequences on the pharmacodynamics of the drug.     

Pharmacokinetics of meloxicam after intravenous,intramuscular and oral administration of a single dose to African grey parrots (Psittacus erithacus)

Meloxicam is a nonsteroidal anti‐inflammatory drug commonly used in avian species. In this study, the pharmacokinetic parameters for meloxicam were determined following single intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administrations of the drug (1 mg/kg·b.w.) in adult African grey parrots (Psittacus erithacus; n = 6). Serial plasma samples were collected and meloxicam concentrations were determined using a validated high‐performance liquid chromatography assay. A noncompartmental pharmacokinetic analysis was performed. No undesirable side effects were observed during the study. After i.v. administration, the volume of distribution, clearance and elimination half‐life were 90.6 ± 4.1 mL/kg, 2.18 ± 0.25 mL/h/kg and 31.4 ± 4.6 h, respectively. The peak mean ± SD plasma concentration was 8.32 ± 0.95 μg/mL at 30 min after i.m. administration. Oral administration resulted in a slower absorption (t_max = 13.2 ± 3.5 h; C_max = 4.69 ± 0.75 μg/mL) and a lower bioavailability (38.1 ± 3.6%) than for i.m. (78.4 ± 5.5%) route. At 24 h, concentrations were 5.90 ± 0.28 μg/mL for i.v., 4.59 ± 0.36 μg/mL for i.m. and 3.21 ± 0.34 μg/mL for p.o. administrations and were higher than those published for Hispaniolan Amazon parrots at 12 h with predicted analgesic effects.     

Pharmacokinetics of meloxicam in mature swine after intravenous and oral administration

The purpose of this study was to compare the pharmacokinetics of meloxicam in mature swine after intravenous (i.v.) and oral (p.o.) administration. Six mature sows (mean bodyweight ± standard deviation = 217.3 ± 65.68 kg) were administered an i.v. or p.o. dose of meloxicam at a target dose of 0.5 mg/kg in a cross‐over design. Plasma samples collected up to 48 h postadministration were analyzed by high‐pressure liquid chromatography and mass spectrometry (HPLC‐MS) followed by noncompartmental pharmacokinetic analysis. Mean peak plasma concentration (C_MAX) after p.o. administration was 1070 ng/mL (645–1749 ng/mL). T_MAX was recorded at 2.40 h (0.50–12.00 h) after p.o. administration. Half‐life (T½ λ_z) for i.v. and p.o. administration was 6.15 h (4.39–7.79 h) and 6.83 h (5.18–9.63 h), respectively. The bioavailability (F) for p.o. administration was 87% (39–351%). The results of this study suggest that meloxicam is well absorbed after oral administration.     

Pharmacokinetics of ketorolac tromethamine in horses after intravenous,intramuscular, and oral single‐dose administration

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are an integral component of equine analgesia, yet currently available NSAIDs are both limited in their analgesic efficacy and have adverse effects. The NSAID ketorolac tromethamine (KT) is widely used in humans as a potent morphine‐sparing analgesic drug but has not been fully evaluated in horses. The purpose of this study was to determine the pharmacokinetic profile of KT in horses after intravenous (i.v.), intramuscular (i.m.), and oral (p.o.) administration. Nine healthy adult horses received a single 0.5‐mg/kg dose of KT via each route of administration. Plasma was collected up to 48 h postadministration and analyzed for KT concentration using HPLC/MS/MS. Noncompartmental analysis of i.v. dosage indicated a mean plasma clearance of 8.4 (mL/min)/kg and an estimated mean volume of distribution at steady‐state of 0.77 L/kg. Noncompartmental analysis of i.v., i.m., and p.o. dosages indicated mean residence times of 2.0, 2.6, and 7.1 h, respectively. The drug was rapidly absorbed after i.m. and p.o. administration, and mean bioavailability was 71% and 57% for i.m. and p.o. administration, respectively. Adverse effects were not observed after i.v., i.m., and p.o. administration. More studies are needed to evaluate the analgesic and anti‐inflammatory properties of KT in horses.     

Pharmacokinetics of sanguinarine,chelerythrine, and their metabolites in broiler chickens following oral and intravenous administration

Sanguinarine (SA) and chelerythrine (CHE) are the main active components of the phytogenic livestock feed additive, Sangrovit®. However, little information is available on the pharmacokinetics of Sangrovit® in poultry. The goal of this work was to study the pharmacokinetics of SA, CHE, and their metabolites, dihydrosanguinarine (DHSA) and dihydrochelerythrine (DHCHE), in 10 healthy female broiler chickens following oral (p.o.) administration of Sangrovit® and intravenous (i.v.) administration of a mixture of SA and CHE. The plasma samples were processed using two different simple protein precipitation methods because the parent drugs and metabolites are stable under different pH conditions. The absorption and metabolism of SA following p.o. administration were fast, with half‐life (t_1/2) values of 1.05 ± 0.18 hr and 0.83 ± 0.10 hr for SA and DHSA, respectively. The maximum concentration (C_max) of DHSA (2.49 ± 1.4 μg/L) was higher that of SA (1.89 ± 0.8 μg/L). The area under the concentration vs. time curve (AUC) values for SA and DHSA were 9.92 ± 5.4 and 6.08 ± 3.49 ng/ml hr, respectively. Following i.v. administration, the clearance (CL) of SA was 6.79 ± 0.63 (L·h^?1·kg^?1) with a t_1/2 of 0.34 ± 0.13 hr. The AUC values for DHSA and DHCHE were 7.48 ± 1.05 and 0.52 ± 0.09 (ng/ml hr), respectively. These data suggested that Sangrovit® had low absorption and bioavailability in broiler chickens. The work reported here provides useful information on the pharmacokinetic behavior of Sangrovit® after p.o. and i.v. administration in broiler chickens, which is important for the evaluation of its use in poultry.     

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.     

Toxicokinetics and absolute oral bioavailability of melamine in broiler chickens

The objective of this study was to investigate the toxicokinetic characteristics of melamine in broilers due to the limited information available for livestock. Melamine was then administered to broiler chickens at an intravenous (i.v.) or oral (p.o.) dosage of 5.5 mg/kg of body weight, and plasma samples were collected up to 48 h. The concentration of melamine in each plasma sample was analyzed using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Melamine was measurable up to 24 h after i.v. and p.o. administration. A one‐compartment model was developed to describe the toxicokinetics of melamine in broilers. Following i.v. administration, the values for the elimination half‐life (t_1/2β), the volume of distribution (V_d), and the clearance (CL) were 4.42 ± 1.02 h, 00.52 ± 0.18 L/kg, and 0.08 ± 0.01 L/h/kg, respectively. The absolute oral bioavailability (F) was 95.63 ± 3.54%. The results suggest that most of the administered melamine is favorably absorbed from the alimentary tract and rapidly cleared by the kidneys in broiler chickens.     

Pharmacokinetics of tolfenamic acid in green sea turtles (Chelonia mydas) after intravenous and intramuscular administration

The present study aimed to evaluate the pharmacokinetic features of tolfenamic acid (TA) in green sea turtles, Chelonia mydas. Green sea turtles were administered single either intravenous (i.v.) or intramuscular (i.m.) injection of TA, at a dose of 4 mg/kg body weight (b.w.). Blood samples were collected at preassigned times up to 168 hr. The plasma concentrations of TA were measured using a validated liquid chromatography tandem mass spectrometry method. Tolfenamic acid plasma concentrations were quantifiable for up to 168 hr after i.v. and i.m. administration. The concentration of TA in the experimental green sea turtles with respect to time was pharmacokinetically analyzed using a noncompartment model. The C_max values of TA were 55.01 ± 8.34 µg/ml following i.m. administration. The elimination half-life values were 32.76 ± 4.68 hr and 53.69 ± 3.38 hr after i.v. and i.m. administration, respectively. The absolute i.m. bioavailability was 72.02 ± 10.23%, and the average binding percentage of TA to plasma protein was 19.43 ± 6.75%. Based on the pharmacokinetic data, the i.m. administration of TA at a dosage of 4 mg/kg b.w. might be sufficient to produce a long-lasting anti-inflammatory effect (7 days) for green sea turtles. However, further studies are needed to determine the clinical efficacy of TA for treatment of inflammatory disease after single and multiple dosages.     

Pharmacokinetics and bioavailability of tildipirosin in rabbits following single-dose intravenous and intramuscular administration

The objective of this study was to determine the pharmacokinetics of tildipirosin in rabbits after a single intravenous (i.v.) and intramuscular (i.m.) injection at a dose of 4 mg/kg. Twelve white New Zealand rabbits were assigned to a randomized, parallel trial design. Blood samples were collected prior to administration and up to 14 days postadministration. Plasma concentrations of tildipirosin were quantified using a validated ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. The pharmacokinetic parameters were calculated using a noncompartmental model in WinNonlin 5.2 software. Following i.v. and i.m. administration, the elimination half-life (T_1/2λ) was 81.17 ± 9.28 and 96.68 ± 15.37 hr, respectively, and the mean residence time (MRT_last) was 65.44 ± 10.89 and 67.06 ± 10.49 hr, respectively. After i.v. injection, the plasma clearance rate (Cl) and volume of distribution at steady state (V_dss) were 0.28 ± 0.10 L kg^-1 h⁻¹ and 17.78 ± 5.15 L/kg, respectively. The maximum plasma concentration (C_max) and time to reach maximum plasma concentration (T_max) after i.m. administration were 836.2 ± 117.9 ng/ml and 0.33 ± 0.17 hr, respectively. The absolute bioavailability of i.m. administration was 105.4%. Tildipirosin shows favorable pharmacokinetic characteristics in rabbits, with fast absorption, extensive distribution, and high bioavailability. These findings suggest that tildipirosin might be a potential drug for the prevention and treatment of respiratory diseases in rabbits.     

The pharmacokinetics of DPH after the administration of a single intravenous or intramuscular dose in healthy dogs

The objective of this study was to determine the pharmacokinetics of diphenhydramine (DPH) in healthy dogs following a single i.v. or i.m. dose. Dogs were randomly allocated in two treatment groups and received DPH at 1 mg/kg, i.v., or 2 mg/kg, i.m. Blood samples were collected serially over 24 h. Plasma concentrations of DPH were determined by high‐performance liquid chromatography, and noncompartmental pharmacokinetic analysis was performed with the commercially available software. Cardio‐respiratory parameters, rectal temperature and effects on behaviour, such as sedation or excitement, were recorded. Diphenhydramine Cl_area, Vd_area and T_1/2 were 20.7 ± 2.9 mL/kg/min, 7.6 ± 0.7 L/kg and 4.2 ± 0.5 h for the i.v. route, respectively, and Cl_area/F, Vd_area/F and T_1/2 20.8 ± 2.7 mL/kg/min, 12.3 ± 1.2 L/kg and 6.8 ± 0.7 h for the i.m. route, respectively. Bioavailability was 88% after i.m. administration. No significant differences were found in physiological parameters between groups or within dogs of the same group, and values remained within normal limits. No adverse effects or changes in mental status were observed after the administration of DPH. Both routes of administration resulted in DPH plasma concentrations which exceeded levels considered therapeutic in humans.     

Dispositions and tissue depletion of melamine in ducks

To evaluate the toxicokinetics and persistence of residues of melamine (MEL) in ducks, MEL was administered intravenously (i.v.) or orally (p.o.) to ducks at a dosage of 5.5 mg/kg body weight. The concentration of MEL in the plasma and various tissues was detected using HPLC equipped with an ultraviolet detector. The plasma concentration of MEL in ducks was determined up to 12 h after both i.v. and p.o. administrations. The average value of elimination half‐life (t_1/2β) of MEL was 2.16 ± 0.37 and 2.01 ± 0.56 h after i.v. and p.o. administration, respectively. The absolute p.o. bioavailability was 90.79%. MEL was measurable in the liver and kidney after p.o. administration with maximum levels of 15.80 ± 1.81 and 15.49 ± 2.12 μg/g at 6 h, respectively. The results suggest that most of the administered MEL is efficiently absorbed from the gastro intestinal tract, and it has the ability to distribute into various tissues of the duck.     

Pharmacokinetics of tolfenamic acid in Hawksbill turtles (Eretmochelys imbricata) after single intravenous and intramuscular administration

To the best of our knowledge, limited pharmacokinetic information to establish suitable therapeutic plans is available for Hawksbill turtles. Therefore, the present study aimed to assess the pharmacokinetic features of tolfenamic acid (TA) in Hawksbill turtles, Eretmochelys imbricata, after single intravenous (i.v.) and intramuscular (i.m.) administration at dosage 4 mg/kg body weight (b.w.). The study (parallel design) used 10 Hawksbill turtles randomly divided into equal groups. Blood samples were collected at assigned times up to 144 hr. The concentrations of TA in plasma were quantified by a validated liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS). The concentration of TA in the experimental turtles with respect to time was pharmacokinetically analyzed using a noncompartment model. The C_max values of TA were 89.33 ± 6.99 µg/ml following i.m. administration. The elimination half-life values were 38.92 ± 6.31 hr and 41.09 ± 9.32 hr after i.v. and i.m. administration, respectively. The absolute i.m. bioavailability was 94.46%, and the average binding percentage of TA to plasma protein was 31.39%. TA demonstrated a long half-life and high bioavailability following i.m. administration. Therefore, the i.m. administration is recommended for use in clinical practice because it is both easier to perform and provides similar plasma concentrations to the i.v. administration. However, further studies are needed to determine the clinical efficacy of TA for treatment of inflammatory disease after single and multiple dosages.     

Pharmacokinetics of danofloxacin and N‐desmethyldanofloxacin in adult horses and their concentration in synovial fluid

The objectives of this study were to investigate the pharmacokinetics of danofloxacin and its metabolite N‐desmethyldanofloxacin and to determine their concentrations in synovial fluid after administration by the intravenous, intramuscular or intragastric routes. Six adult mares received danofloxacin mesylate administered intravenously (i.v.) or intramuscularly (i.m.) at a dose of 5 mg/kg, or intragastrically (IG) at a dose of 7.5 mg/kg using a randomized Latin square design. Concentrations of danofloxacin and N‐desmethyldanofloxacin were measured by UPLC‐MS/MS. After i.v. administration, danofloxacin had an apparent volume of distribution (mean ± SD) of 3.57 ± 0.26 L/kg, a systemic clearance of 357.6 ± 61.0 mL/h/kg, and an elimination half‐life of 8.00 ± 0.48 h. Maximum plasma concentration (C_max) of N‐desmethyldanofloxacin (0.151 ± 0.038 μg/mL) was achieved within 5 min of i.v. administration. Peak danofloxacin concentrations were significantly higher after i.m. (1.37 ± 0.13 μg/mL) than after IG administration (0.99 ± 0.1 μg/mL). Bioavailability was significantly higher after i.m. (100.0 ± 12.5%) than after IG (35.8 ± 8.5%) administration. Concentrations of danofloxacin in synovial fluid samples collected 1.5 h after administration were significantly higher after i.v. (1.02 ± 0.50 μg/mL) and i.m. (0.70 ± 0.35 μg/mL) than after IG (0.20 ± 0.12 μg/mL) administration. Monte Carlo simulations indicated that danofloxacin would be predicted to be effective against bacteria with a minimum inhibitory concentration (MIC) ≤0.25 μg/mL for i.v. and i.m. administration and 0.12 μg/mL for oral administration to maintain an area under the curve:MIC ratio ≥50.     

Pharmacokinetics of grapiprant,a selective EP4 prostaglandin PGE2 receptor antagonist,after 2 mg/kg oral and i.v. administrations in cats

Drugs that provide effective analgesia in cats are limited. The aim of the study was to assess the pharmacokinetics of grapiprant after 2 mg/kg administration via p.o. and i.v. routes in cats. Six healthy adult cats were used according to an open, single‐dose, two‐treatment, two‐period, randomized cross‐over design. Cats were assigned to two treatment groups and administered with 2 mg/kg of grapiprant (pure powder) through p.o. and i.v. administration. Blood samples were collected at preassigned times and analysed by a validated HPLC method. After both administrations, grapiprant concentrations were detectable in plasma for up to 24 hr in five of six animals. The critical parameters including clearance (173.2 ml hr^?1 kg^?1, range 120–326 ml hr^?1 kg^?1) and volume of distribution (918 ml/kg, range 611–1608 ml/kg) were calculated from the i.v. group. The mean oral F% was low (39.6% range 31.5%–45.2%). If the assumption that the minimal effective concentration in dogs (164 ng/ml) applies in cats too, grapiprant orally administered at 2 mg/kg might be effective for 10 hr. Further studies are necessary to establish the minimal effective concentration in this animal species.     

Pharmacokinetics of tildipirosin in beagle dogs

The objective of this study was to investigate the pharmacokinetic profile of tildipirosin (TD) in 24 beagle dogs following intravenous (i.v.) and intramuscular (i.m.) administration, respectively, at 2, 4, and 6 mg/kg. Plasma samples at certain time points (0–14 days) were collected, and the concentrations of drug were quantified by UPLC‐MS/MS. Plasma concentration–time data and relevant parameters were described by noncompartmental through WinNonlin 6.4 software. After single i.m. injection at 2, 4, and 6 mg/kg body weight, mean maximum concentration (C_max) was 412.73 ± 76.01, 1,051 ± 323, and 1,061 ± 352 ng/ml, respectively. Mean time to reach C_max was 0.36 ± 0.2, 0.08 ± 0.00, and 0.13 ± 0.07 hr after i.m. injection at 2, 4, and 6 mg/kg, respectively. The mean value of T_1/2λz for i.m. administration at doses of 2, 4, and 6 mg/kg was 71.39 ± 28.42, 91 .33 ± 50.02, and 96.43 ± 45.02 hr, respectively. The mean residence times were 63.81 ± 10.96, 35.83 ± 15.13, and 38.18 ± 16.77 hr for doses of 2, 4, and 6 mg/kg, respectively. These pharmacokinetic characteristics after i.m. administration indicated that TD could be rapidly distributed into tissues on account of the high lipid solubility and then released into plasma. In addition, the absolute bioavailability of 2 mg/kg after i.m. injection was 112%. No adverse effects were observed after i.v. and i.m. administration.     

Pharmacokinetics of vitacoxib in rabbits after intravenous and oral administration

This study describes the pharmacokinetics of vitacoxib in healthy rabbits following administration of 10 mg/kg intravenous (i.v.) and 10 mg/kg oral. Twelve New Zealand white rabbits were randomly allocated to two equally sized treatment groups. Blood samples were collected at predetermined times from 0 to 36 hr after treatment. Plasma drug concentrations were determined using UPLC‐MS/MS. Pharmacokinetic analysis was completed using noncompartmental methods via WinNonlin^? 6.4 software. The mean concentration area under curve (AUC_last) for vitacoxib was determined to be 11.0 ± 4.37 μg hr/ml for i.v. administration and 2.82 ± 0.98 μg hr/ml for oral administration. The elimination half‐life (T_1/2λz) was 6.30 ± 2.44 and 6.30 ± 1.19 hr for the i.v. and oral route, respectively. The C_max (maximum plasma concentration) and T_max (time to reach the observed maximum (peak) concentration at steady‐state) following oral application were 189 ± 83.1 ng/ml and 6.58 ± 3.41 hr, respectively. Mean residence time (MRT_last) following i.v. injection was 6.91 ± 3.22 and 11.7 ± 2.12 hr after oral administration. The mean bioavailability of oral administration was calculated to be 25.6%. No adverse effects were observed in any rabbit. Further studies characterizing the pharmacodynamics of vitacoxib are required to develop a formulation of vitacoxib for rabbits.     

Pharmacokinetics and bioavailability of tildipirosin following intravenous and subcutaneous administration in sheep

Tildipirosin is a semi‐synthetic macrolide antibiotic commonly used in cattle and swine to treat bacterial pneumonia. The objective of this study was to investigate the pharmacokinetic profile of tildipirosin after a single intravenous (i.v.) and subcutaneous (s.c.) administration in healthy lambs. Eighteen lambs were randomly divided into three groups (n = 6 each). Lambs received a single s.c. dose of tildipirosin at 4 and 6 mg/kg b.w. in group 1 and 2, respectively. Lambs in group 3 received a single i.v. dose of tildipirosin at 4 mg/kg b.w. Blood samples were collected at 0, 0.5, 0.75, 1.5, 2, 3, 4, 6, 8, 10, 24, 36, 48 hr, and every 24 hr to day 21, and thereafter at day 28 posttildipirosin administration. The plasma concentrations of tildipirosin were determined using high‐performance liquid chromatography with tandem mass spectrometry detection (LC?MS?MS). All lambs appeared to tolerate both the intravenous and subcutaneous injection of tildipirosin. Following i.v. administration, the elimination half‐life (T_1/2), mean residence time (MRT), volume of distribution (Vd/F), and total body clearance (Cl/F) were 119.6 ± 9.0 hr, 281.9 ± 25.7 hr, 521.1 ± 107.2 L, and 2.9 ± 0.5 L/hr, respectively. No significant differences in C_max (657.0 ± 142.8 and 754.6 ± 227.1 ng/ml), T_max (1.21 ± 0.38 and 1.35 ± 0.44 hr), T_1/2 (144 ± 17.5, 156.5 ± 33.4 hr), and MRT (262.0 ± 30.2 and 250.6 ± 54.5 hr) were found in tildipirosin after s.c. dosing at 4 and 6 mg/kg b.w., respectively. The absolute bioavailability (F) of tildipirosin was 71.5% and 75.3% after s.c. administration of 4 and 6 mg/kg b.w., respectively. In conclusion, tildipirosin was rapidly absorbed and slowly eliminated after a single s.c. administration in healthy lambs. Tildipirosin could be used for the treatment and prevention of respiratory bacterial infections in sheep. However, further in vitro and in vivo studies to determine the efficacy and safety are warranted. To our knowledge, this is the first study to determine the tildipirosin pharmacokinetic parameters in sheep plasma.