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.     

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 norfloxacin after intravenous,intramuscular and subcutaneous administration to rabbits

The disposition kinetics of norfloxacin, after intravenous, intramuscular and subcutaneous administration was determined in rabbits at a single dose of 10 mg/kg. Six New Zealand white rabbits of both sexes were treated with aqueous solution of norfloxacin (2%). A cross‐over design was used in three phases (2 × 2 × 2), with two washout periods of 15 days. Plasma samples were collected up to 72 hr after treatment, snap‐frozen at ?45°C and analysed for norfloxacin concentrations using high‐performance liquid chromatography. The terminal half‐life for i.v., i.m. and s.c. routes was 3.18, 4.90 and 4.16 hr, respectively. Clearance value after i.v. dosing was 0.80 L/h·kg. After i.m. administration, the absolute bioavailability was (mean ± SD ) 108.25 ± 12.98% and the C_max was 3.68 mg/L. After s.c. administration, the absolute bioavailability was (mean ± SD ) 84.08 ± 10.36% and the C_max was 4.28 mg/L. As general adverse reactions were not observed in any rabbit and favourable pharmacokinetics were found, norfloxacin at 10 mg/kg after i.m. and s.c. dose could be effective in rabbits against micro‐organisms with MIC ≤0.14 or 0.11 μg/mL , respectively.     

Pharmacokinetics of benzydamine in dairy cows following intravenous or intramuscular administration

Five lactating cows were given benzydamine hydrochloride by rapid intravenous (0.45 mg/kg) and by intramuscular (0.45 and 1.2 mg/kg) injection in a crossover design. The bioavailability, pharmacokinetic parameters and excretion in milk of benzydamine were evaluated. After intravenous administration, the disposition kinetics of benzydamine was best described using a two-compartment open model. Drug disposition and elimination were fast (t _1/2: 11.13±3.76 min;t _1/2: 71.98±24.75 min; MRT 70.69±11.97 min). Benzydamine was widely distributed in the body fluids and tissues (V _d(area): 3.549±1.301 L/kg) and characterized by a high value for body clearance (33.00±5.54 ml/kg per min). After intramuscular administration the serum concentration-time curves fitted a one-compartment open model. Following a dose of 0.45 mg/kg, theC _max value was 38.13±4.2 ng/ml at at _max of 67.13±4.00 min; MAT and MRT were 207.33±22.64 min and 278.01±12.22 min, respectively. Benzydamine bioavailability was very high (92.07%±7.08%). An increased intramuscular dose (1.2 mg/kg) resulted in longer serum persistence (MRT 420.34±86.39 min) of the drug, which was also detectable in milk samples collected from both the first and second milking after treatment.Abbreviations HPLC high-pressure liquid chromatography - IC50 concentration to inhibit the activity of an organism by 50% - IM intramuscular(ly) - IV intravenous(ly) - NSAID non-steroidal antiinflammatory drugs - pK _a negative logarithm of the ionization constant (K _a) of a drug; other abbreviations are listed in footnotes to tables     

泰地罗新注射液在猪体内的药代动力学及绝对生物利用度研究

为了研究泰地罗新注射液肌内注射和静脉注射在猪体内的药动学特征和绝对生物利用度,16只健康猪采用随机单剂量、平行试验设计,分别以4 mg/kg BW肌内注射和以1 mg/kg BW静脉注射泰地罗新注射液。采用超高效液相色谱-串联质谱法测定猪血浆中泰地罗新的浓度,以药动学分析软件WinNolin 6.4非房室模型计算药动学参数。结果显示,猪肌内注射泰地罗新注射液的药动学参数分别为Tmax(0.58±0.36)h,Cmax(0.88±0.17)μg/ml,AUClast(11.00±4.05)μg.h/mL,T1/2λz(33.58±22.01) h,MRTlast(35.60±10.00 )h。猪静脉注射泰地罗新注射液的药动学参数分别为AUClast(3.56±1.62)μg.h/mL,T1/2λz(50.91±23.47)h,MRTlast(37.53±4.52 )h,Vz(17.59±8.09)L/kg,Cl(0.31±0.14)L/h.kg。肌内注射泰地罗新注射液的绝对生物利用度77.15%,在猪体内的药动学特征是吸收迅速,血浆达峰时间短,消除半衰期长,绝对生物利用度高。     

Pharmacokinetics of diclofenac in sheep following intravenous and intramuscular administration

OBJECTIVES: The aim of this work was to examine the pharmacokinetics of diclofenac (DCLF) in sheep after intravenous (IV) and intramuscular (IM) dosing. ANIMALS: Healthy male Najdi sheep. MATERIALS AND METHODS: Diclofenac (1 mg kg(-1)) was administered to ten clinically healthy-male Najdi sheep IV or IM (n = 5 each). Blood samples (5 mL) were collected and serum was separated for drug analysis by high-performance liquid chromatography with UV detection. Diclofenac pharmacokinetic parameters were determined by noncompartmental analysis. RESULTS: Diclofenac is quickly eliminated from sheep with a terminal T(1/2lambda) of 2-3 hours for both routes of administration. Total DCLF clearance after IV and IM administration was 87.86 +/- 24.10 and 85.69 +/- 40.76 mL kg(-1) hour(-1) respectively. The absolute bioavailability of IM DCLF appears to be approximately 100%. CONCLUSIONS AND CLINICAL RELEVANCE: The drug should be administered two to three times daily in sheep by IM or IV injection to maintain therapeutic concentrations. Additional studies are needed to evaluate the route of elimination of DCLF in sheep including metabolites formation and the significance of enterohepatic circulation.     

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.     

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 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 enrofloxacin following intravenous and intramuscular administration in Angora rabbits

The pharmacokinetic behaviour and bioavailability of enrofloxacin (ENR) were determined after single intravenous (iv) and intramuscular (im) administrations of 5mg/kg bw to six healthy adult Angora rabbits. Plasma ENR concentrations were measured by high performance liquid chromatography. The pharmacokinetic data were best described by a two-compartment open model. ENR pharmacokinetic parameters were similar (p>0.05) for iv and im administrations in terms of AUC0-infinity, t1/2beta and MRT. ENR was rapidly (t1/2a, 0.05 h) and almost completely (F, 87%) absorbed after im injection. In conclusion, the pharmacokinetic properties of ENR following iv and im administration in Angora rabbits are similar to other rabbit breeds, and once or twice daily iv and im administrations of ENR at the dose of 5mg/kg bw, depending upon the causative pathogen and/or severity of disorders, may be useful in treatment of infectious diseases caused by sensitive pathogens in Angora rabbits.     

Pharmacokinetics of orbifloxacin in crucian carp (Carassius auratus) after intravenous and intramuscular administration

The pharmacokinetics of orbifloxacin was studied after a single dose (7.5 mg/kg) of intravenous or intramuscular administration to crucian carp (Carassius auratus ) reared in freshwater at 25°C. Plasma samples were collected from six fish per sampling point. Orbifloxacin concentrations were determined by high‐performance liquid chromatography with a 0.02 μg/ml limit of detection, then were subjected to noncompartmental analysis. After intravenous injection, initial concentration of 5.83 μg/ml, apparent elimination rate constant (λ_z) of 0.039 hr^?1, apparent elimination half‐life (T_1/2λz) of 17.90 hr, systemic total body clearance (Cl) of 75.47 ml hr^?1 kg^?1, volume of distribution (Vz) of 1,948.76 ml/kg, and volume of distribution at steady‐state (Vss) of 1,863.97 ml/kg were determined, respectively. While after intramuscular administration, the λ_z, T _1/2λz, mean absorption time (MAT ), absorption half‐life (T _1/2ka), and bioavailability were determined as 0.027 hr^?1, 25.69, 10.26, 7.11 hr, and 96.46%, respectively, while the peak concentration was observed as 3.11 ± 0.06 μg/ml at 2.0 hr. It was shown that orbifloxacin was completely but relatively slowly absorbed, extensively distributed, and slowly eliminated in crucian carp, and an orbifloxacin dosage of 10 mg/kg administered intravenously or intramuscularly would be expected to successfully treat crucian carp infected by strains with MIC values ≤0.5 μg/ml.     

Pharmacokinetics of detomidine and its metabolites following intravenous and intramuscular administration in horses

Reasons for performing study: Detomidine is commonly used i.v. for sedation and analgesia in horses, but the pharmacokinetics and metabolism of this drug have not been well described. Objectives: To describe the pharmacokinetics of detomidine and its metabolites, 3‐hydroxy‐detomidine (OH‐detomidine) and detomidine 3‐carboxylic acid (COOH‐detomidine), after i.v. and i.m. administration of a single dose to horses. Methods: Eight horses were used in a balanced crossover design study. In Phase 1, 4 horses received a single dose of i.v. detomidine, administered 30 μg/kg bwt and 4 a single dose i.m. 30 üg/kg bwt. In Phase 2, treatments were reversed. Plasma detomidine, OH‐detomidine and COOH‐detomidine were measured at predetermined time points using liquid chromatography‐mass spectrometry. Results: Following i.v. administration, detomidine was distributed rapidly and eliminated with a half‐life (t_1/2(el)) of approximately 30 min. Following i.m. administration, detomidine was distributed and eliminated with t_1/2(el) of approximately one hour. Following, i.v. administration, detomidine clearance had a mean, median and range of 12.41, 11.66 and 10.10–18.37 ml/min/kg bwt, respectively. Detomidine had a volume of distribution with the mean, median and range for i.v. administration of 470, 478 and 215–687 ml/kg bwt, respectively. OH‐detomidine was detected sooner than COOH‐detomidine; however, COOH‐detomidine had a much greater area under the curve. Conclusions and potential relevance: These pharmacokinetic parameters provide information necessary for determination of peak plasma concentrations and clearance of detomidine in mature horses. The results suggest that, when a longer duration of plasma concentration is warranted, the i.m. route should be considered.     

Pharmacokinetics and relative bioavailability of tiamulin in broiler chicken as influenced by different routes of administration

The bioavailability and pharmacokinetic disposition of tiamulin in broiler chicken were investigated after administration through the crop, drinking water, and feed at 40 mg/kg body weight. Residues of tiamulin in tissues of broiler chicken were also assessed. Plasma and tissue concentrations of tiamulin were analyzed by reverse‐phase high‐performance liquid chromatography (HPLC) method. Plasma concentration–time data were described by the non‐compartmental model for all three routes, and pharmacokinetic parameters were calculated. There were no significant differences (p > 0.05) in pharmacokinetic parameters and mean plasma concentrations of tiamulin between three routes tested (crop, water, and feed), indicating equal efficacy. Tiamulin residues in edible tissues (muscles, skin, and fat) were lower than the advocated maximum residue limit (MRL of 0.1 µg/g and that of liver was 1 µg/g) on the 3rd day. No traces were found on the 5th day after drug administration. This indicated that the withdrawal period (less than 5 days) is very short, which makes it safer. This study shows that tiamulin can be used with equal efficacy through all routes of administration in broiler chicken (crop, water, and feed).     

Pharmacokinetics of single-dose intravenous or intramuscular administration of gentamicin in roosters

Healthy mature roosters (n = 10) were given gentamicin (5 mg/kg of body weight, IV) and, 30 days later, another dose IM. Serum concentrations of gentamicin were determined over 60 hours after each drug dosing, using a radioimmunoassay. Using nonlinear least-square regression methods, the combined data of IV and IM treatments were best fitted by a 2-compartment open model. The mean distribution phase half-life was 0.203 +/- 0.075 hours (mean +/- SD) and the terminal half-life was 3.38 +/- 0.62 hours. The volume of the central compartment was 0.0993 +/- 0.0097 L/kg, volume of distribution at steady state was 0.209 +/- 0.013 L/kg, and the total body clearance was 46.5 +/- 7.9 ml/h/kg. Intramuscular absorption was rapid, with a half-life for absorption of 0.281 +/- 0.081 hours. The extent of IM absorption was 95 +/- 18%. Maximal serum concentration of 20.68 +/- 2.10 micrograms/ml was detected at 0.62 +/- 0.18 hours after the dose. Kinetic calculations predicted that IM injection of gentamicin at a dosage of 4 mg/kg, q 12 h, and 1.5 mg/kg, q 8 h, would provide average steady-state serum concentrations of 6.82 and 3.83 micrograms/ml, with minimal steady-state serum concentrations of 1.54 and 1.50 micrograms/ml and maximal steady-state serum concentrations of 18.34 and 7.70 micrograms/ml, respectively.     

口服硫酸安普霉素在猪体内的药代动力学和生物利用度研究

对 5头健康猪口服和静脉注射国产硫酸安普霉素 ,研究其在猪体内的药代动力学和生物利用度。用微生物法测定血清药物浓度 ,结果平均回收率为 99.0 3%,血清最低检测浓度为 0 .0 5 μg/ ml,日内日间变异系数为 2 .2 %～ 5 .0 %,且血清浓度在0 .0 5～ 3μg/ m l范围呈良好线性关系 (r=0 .996 5 )。以 2 0 mg/ kg口服和以 2 0 mg/ kg静脉注射硫酸安普霉素后 ,经 Mcpkp药代动力学计算机程序处理 ,体内药物运转分别符合开放型一室和二室模型 ,生物半衰期 t1 / 2 分别为 (7.36± 1 .5 2 ) h和 (3.1 7± 0 .75 )h;CLB分别为 4 .82 L / kg· h和 0 .1 6 L / kg· h;AUC值分别为 4 .1 4和 1 30 .6 2。口服 :Cmax为 (0 .2 4± 0 .0 3)μg/ ml;Tp为 (5 .1 2±0 .6 1 ) h;T1 / 2 K为 (7.36± 1 .5 2 ) ;生物利用度 (AUCp.0 / AUCi.v)为 (3.1 92 8± 0 .70 4 4 ) %。上述药代动力学数据为动物临床用药提供有价值的理论依据     

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 clomipramine in dogs following single-dose intravenous and oral administration

OBJECTIVE: To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs after IV or oral administration of a single dose. ANIMALS: 6 male and 6 female Beagles. PROCEDURES: Clomipramine was administered IV (2 mg/kg), PO (4 mg/kg) after food was withheld for 15 hours, and PO (4 mg/kg) within 25 minutes after dogs were fed. Plasma clomipramine and desmethylclomipramine concentrations were measured by use of a gas chromatography with mass-selection method. RESULTS: Time to peak plasma concentrations of clomipramine and desmethylclomipramine following oral administration was 1.2 hours. For clomipramine, after IV administration, elimination half-life was 5 hours, mean residence time was 3 hours, and plasma clearance was 1.4 L/h/kg. Values for mean residence time and terminal half-life following oral administration were similar to values obtained following IV administration, and systemic bioavailability was approximately 20% for clomipramine and 140% for desmethylclomipramine, indicating fast absorption of clomipramine from the gastrointestinal tract and extensive first-pass metabolism. Administration of clomipramine with food did not alter the area under the concentration versus time curve for desmethylclomipramine but resulted in a 25% increase for clomipramine. Clomipramine and desmethylclomipramine were extensively bound (> 96%) to serum proteins. There were no significant differences in area under the concentration versus time curve between male and female dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that there should not be any clinically important differences in efficacy regardless of whether clomipramine is administered with or without food.     

Pharmacokinetics and pharmacodynamics of hydromorphone after intravenous and intramuscular administration in horses

ObjectiveTo compare the pharmacokinetics and pharmacodynamics of hydromorphone in horses after intravenous (IV) and intramuscular (IM) administration.Study designRandomized, masked, crossover design.AnimalsA total of six adult horses weighing [mean ± standard deviation (SD))] 447 ± 61 kg.MethodsHorses were administered three treatments with a 7 day washout. Treatments were hydromorphone 0.04 mg kg^⁻1 IV with saline administered IM (H-IV), hydromorphone 0.04 mg kg^⁻1 IM with saline IV (H-IM), or saline IV and IM (P). Blood was collected for hydromorphone plasma concentration at multiple time points for 24 hours after treatments. Pharmacodynamic data were collected for 24 hours after treatments. Variables included thermal nociceptive threshold, heart rate (HR), respiratory frequency (f_R), rectal temperature, and fecal weight. Data were analyzed using mixed-effects linear models. A p value of less than 0.05 was considered statistically significant.ResultsThe mean ± SD hydromorphone terminal half-life (t_1/2), clearance and volume of distribution of H-IV were 19 ± 8 minutes, 79 ± 12.9 mL minute^⁻1 kg^⁻1 and 1125 ± 309 mL kg^⁻1. The t_1/2 was 26.7 ± 9.25 minutes for H-IM. Area under the curve was 518 ± 87.5 and 1128 ± 810 minute ng mL^⁻1 for H-IV and H-IM, respectively. The IM bioavailability was 217%. The overall thermal thresholds for both H-IV and H-IM were significantly greater than P (p < 0.0001 for both) and baseline (p = 0.006). There was no difference in thermal threshold between H-IV and H-IM. No difference was found in physical examination variables among groups or in comparison to baseline. Fecal weight was significantly less than P for H-IV and H-IM (p = 0.02).Conclusions and clinical relevanceIM hydromorphone has high bioavailability and provides a similar degree of antinociception to IV administration.IM hydromorphone in horses provides a similar degree and duration of antinociception to IV administration.