Research Note: Pharmacokinetics of bromhexine hydrochloride in broilers after single oral and intravenous administration.

The current study aimed to investigate the pharmacokinetics of bromhexine hydrochloride in broilers after single intravenous (IV) and oral (PO) administration at 2.5 mg/kg body weight (BW). The trial adopted a randomized, parallel-controlled design, where 20 twelve-wk-old broilers were randomly assigned to either the PO or IV group. Blood samples were collected at predetermined time points, and plasma was further separated for analysis. The bromhexine hydrochloride concentrations in plasma samples were determined using an ultra-performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method. Noncompartmental analysis (NCA) using Phoenix software was conducted to analyze the concentration versus time data of bromhexine hydrochloride in every chicken. Subsequently, the main pharmacokinetic parameters between the 2 groups were statistically analyzed using SPSS software. Results from NCA revealed that after oral administration at 2.5 mg/kg BW, bromhexine hydrochloride exhibited slow absorption, reaching an average peak concentration of 32.72 ng/mL at 1.78 h. However, incomplete absorption was observed, with an absolute bioavailability of only 20.06% ± 10.84%. Additionally, bromhexine hydrochloride displayed wide distribution, with a steady-state distribution volume (VSS) of 22.55 ± 13.45 L/kg, and slow elimination, with a clearance (Cl) of 1.52 ± 0.38 L/h/kg. Furthermore, gender effects were assessed on the pharmacokinetics of bromhexine hydrochloride in broilers, revealing better absorption in male broilers compared to females. This disparity may be attributed to the faster blood flow and richer blood volume typically found in male broilers.

The efficacy of intravenous application of the Mycobacterium Cell Wall Fraction (AMPLIMUNE) in the treatment of subclinical mastitis caused by S. Aureus.

The aim of the study was to investigate the effect of the immunostimulant Mycobacterium Cell Wall Fraction (MCWF) on the treatment of S. aureus SCM by intravenous application. The study included 45 HF dairy cows in 2nd and 3rd month after parturition divided into three groups (n = 15 per group): the MC + group - cows with S. aureus SCM treated with MCWF; the MC- group - cows with S. aureus SCM, with no treatment; and the C group - the control group of healthy cow with no treatment. Samples were collected 0th (I sample), 7th (II), and 14th day (III) from the day of SCM diagnosis and on day 21st (IV). A greater influx of leukocytes was confirmed into milk after 7 days after MCWF treatment in MC + group, which was followed by increase of WBC and LYM in blood. These results support the hypothesis of effective action of MCWF, and in quarters with lower-grade infection, bacteriological cure was achieved. The MC- group had a statistically higher concentration of TBARS and CAT activity in milk, while MC + group had lower blood serum LDH activity, which indicates a positive effect of the MCWF application and a lower exposure of the tissue to lipide peroxidation and inflammation caused by S. aureus. The application of MCWF would give new possibilities in the prevention and therapy of mammary gland diseases without fear of the presence of residues and the emergence of bacterial resistance. In future studies, the effects of local and systemic application of MCWF in the treatment of S. aureus SCM should be compared.

Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine (2 µg∙kg-1) in dogs.

This study assessed the pharmacokinetics and pharmacodynamics of low-dose dexmedetomidine after IV bolus in dogs. Six healthy adult dogs (6.8 ± 3.0 kg) received dexmedetomidine (2 µg.kg-1 IV) over 2 min, using an infusion pump. Blood samples were collected totaling 5 h of monitoring. A validated UHPLC-MS/MS method was used to determine the plasma concentration of dexemedetomidine. For pharmacodynamics, HR, RR, oscillometric MBP, Grint END sedation score were evaluated at baseline (T0), every 3 min (T3 to T21), and after 30 (T30) and 60 (T60) minutes, with p < 0.05. T1/2 was 28.28 ± 6.14 min; the area under the curve was 467.44 ± 60.42 ng/mL/min. The total clearance was 5.46 ± 0.41 mL/min/kg, the Vdss was 146.19 ± 21.04 mL/kg, and the C max was 3.13 ± 1.15 ng/mL. HR (bpm) decreased significantly from T6 (79 ± 21) to T21 (78 ± 31) compared to T0 (116 ± 28). RR(mpm) decreased from T3 (43 ± 44) to T60 (41 ± 23), with T0 being 70 ± 48. The MBP (mmHg) increased at T18 (151 ± 34), T21 (152 ± 35), and T30 (140 ± 27), compared to T0 (111 ± 22). Sedation occurred at all times post-bolus, with a maximum peak at T12 (END 8 ± 6). The low dose of dexmedetomidine provided sedation in all animals, characterizing rapid metabolization and elimination. However, cardiovascular effects still may have negative repercussions in dogs with hemodynamic comorbidities, highlighting the caution and individualization of its use in certain patients.

Disposition kinetics of meloxicam in green sea turtles (Chelonia mydas) after intravenous and intramuscular administrations.

The pharmacokinetics were described of meloxicam (MLX) in green sea turtles (Chelonia mydas), following a single intravenous (i.v.) and intramuscular (i.m.) administrations at one of two dosages of 0.1 or 0.2 mg/kg body weight (b.w.). The sample of 20 green sea turtles was divided into four groups (n = 5) using a randomization procedure according to a parallel study design. Blood samples were collected at pre-assigned times up to 168 h. MLX in the plasma was cleaned-up and quantified using a validated high-performance liquid chromatography method with UV detection. The concentration of MLX in the experimental green sea turtles with respect to time was pharmacokinetically analyzed using a non-compartment model. MLX plasma concentrations were quantifiable for up to 72 and 120 h after i.v. at dosages of 0.1 and 0.2 mg/kg b.w., respectively, whereas it was measurable for up to 168 h after i.m. administration at both dosages. The long elimination half-life value of MLX (28 h) obtained in green sea turtles after i.v. administration was consistent with the quite slow clearance rate for both dosages. The average maximum concentration (Cmax ) values of MLX were 1.05 µg/mL and 4.26 µg/mL at dosages of 0.1 and 0.2 mg/kg b.w., respectively, with their elimination half-life values being 37.26 h and 30.64 h, respectively, after i.m. administrations. The absolute i.m. bioavailability was approximately 110%. These results suggested that i.m. administration of MLX at a dosage of 0.2 mg/kg b.w. was likely to be effective for clinical use in green sea turtles (Chelonia mydas). However, further studies are needed to determine the pharmacodynamic properties and clinical efficacy of MLX for the treatment of inflammatory disease after single and multiple dosages.

Correlation of opioid antinociception and hypothermia in dogs-An animal welfare refinement.

The purpose of this study was to assess antinociception and correlation of antinociception and hypothermic effects after intravenous opioids in dogs. Nine healthy male Beagles were enrolled in the study. They were acclimated to a thermal nociceptive device, then received three IV treatments (saline, butorphanol 0.4 mg/kg and methadone 0.5 mg/kg) in a randomized complete block design. Rectal temperature and thermal withdrawals were assessed prior to and 0.5-6 h after drug administration. One dog was excluded due to lack of withdrawal to thermal stimuli. Rectal temperatures were not significantly different between treatments at time 0, but significantly decreased from 0.5 to 5 h for both opioids compared to saline. Withdrawals were significantly decreased, compared to saline, from 0.5 to 4 h for butorphanol and 0.5-5 h for methadone. A significant (p = .0005) and moderate (R2 = .43) correlation between antinociception and hypothermia occurred. Based on these data, intravenous butorphanol (0.4 mg/kg) and methadone (0.5 mg/kg) provided 4 and 5 h of antinociception, respectively. Opioid hypothermia can serve as an easy, noninvasive and humane manner for preclinical assessment of opioid antinociception in dogs prior to evaluation in clinical trials. This is a major refinement in animal welfare for assessing novel opioids, opioid doses and dose intervals in dogs.

Effects of intravenous administration of ascorbic acid (vitamin C) on oxidative status in healthy adult horses.

BACKGROUND: Ascorbic acid (AA) is an antioxidant that might be beneficial for adjunctive treatment of sepsis in horses. The optimal dose and effects on oxidative status are unknown. HYPOTHESIS: Ascorbic acid administration will increase plasma AA concentrations and decrease determinants of reactive oxygen metabolites (dROM), basal and stimulant-induced intraerythrocytic reactive oxygen species (ROS) concentrations, and stimulant-induced neutrophil ROS production, and increase plasma antioxidant capacity (PAC) in a dose-dependent manner. ANIMALS: Eight healthy horses. METHODS: Randomized placebo-controlled crossover study. Each horse received 4 single-dose IV treatments including AA at 25, 50, and 100 mg/kg and saline (placebo) with each treatment separated by ≥1 week. Blood was collected at baseline, 2 and 6 hours for assessment of plasma dROM and PAC via photometer, intraerythrocytic ROS by flow cytometry, and stimulant-induced neutrophil ROS by a fluorometric assay. Plasma AA concentrations were measured by high-performance liquid chromatography/electrochemical detection. RESULTS: Ascorbic acid at 100 mg/kg resulted in decreased dROM 2 hours after treatment (P = .03, 95% CI 5.51-121.2, point estimate 63.3). There was no effect of AA on basal or stimulant-induced intraerythrocytic ROS (P = .88, 95% CI -0.156 to 0.081, point estimate -0.037; P = .93, 95% CI -0.123 to 0.112, point estimate -0.006, respectively), basal or stimulant-induced neutrophil ROS (P ≥ .12, 95% CI -644.9 to 56.2, point estimate -294.4), or PAC (P ≥ .64, 95% CI -1567 to 463.4, point estimate -552.0) at any dose or timepoint. Plasma AA concentrations increased in a dose-dependent manner. CONCLUSIONS AND CLINICAL IMPORTANCE: High-dose administration of AA might provide antioxidant benefits in horses.

Pharmacokinetics of gamma-hydroxybutyric acid in 6-week-old swine (Sus scrofa domesticus) after intravenous and oral administration.

Sedative as well as protective effects during hypoxia have been described for gamma-hydroxybutyric acid (GHB). Six swine (Sus scrofa domesticus) of 6 weeks old were administered NaGHB at a dose of 500 mg/kg intravenously (IV) and 500 and 750 mg/kg orally (PO) in a triple cross-over design. Repeated blood sampling was performed to allow pharmacokinetic analysis of GHB. Whole blood concentration at time point 0 after IV administration was 1727.21 ± 280.73 µg/mL, with a volume of distribution of 339.45 ± 51.41 mL/kg and clearance of 164.94 ± 47.05 mL/(kg h). The mean peak plasma concentrations after PO administration were 326.57 ± 36.70 and 488.01 ± 154.62 µg/mL for 500 mg/kg and 750 mg/kg, respectively. These were recorded at 1.42 ± 0.72 and 1.58 ± 0.58 h after PO dose for GHB 500 mg/kg and 750 mg/kg, respectively. The elimination half-life for IV and PO 500 mg/kg and PO 750 mg/kg dose was respectively 1.33 ± 0.30, 1.16 ± 0.31 and 1.11 ± 0.33 h. The bioavailability (F) for PO administration was 45%. No clinical adverse effects were observed after PO administration. Deep sleep was seen in one animal after IV administration, other animals showed head pressing and ataxia.

Effects of propofol alone or in combination with ketamine on intraocular pressure in unpremedicated dogs.

OBJECTIVE: To determine the effects of propofol (P) alone and in combination with ketamine (KP) at ratios of 1:1, 1:2, and 1:3 on intraocular pressure (IOP) in unpremedicated dogs. ANIMALS STUDIED: A total of 28 cross-bred healthy dogs. PROCEDURES: Dogs were randomly assigned to one of four groups (n = 7 per group) to receive intravenous P or KP at 1:1, 1:2, and 1:3 ratios, respectively. The infusion was administered at 0.6 mg/kg/min for 60 min. IOP, cardiorespiratory variables, rectal temperature (RT), and pedal reflex were recorded every 5 min for 60 min, starting from baseline (BL). RESULTS: There was a statistically significant increase in IOP in all groups: P (p = .011), KP 1:1 (p = .003), KP 1:2 (p = .023), and KP 1:3 (p = .008). The IOP increase was less pronounced in the KP 1:2 group and was only significant (p = .023) at T45 compared with BL. A significant correlation was observed between IOP and SpO2 in P (r = -.215, p = .02), KP 1:2 (r = -.579, p < .01), and KP 1:3 (r = -.402, p < .01) groups. IOP significantly increased due to decreased SpO2 below 86.5% (p < .05). CONCLUSIONS: Propofol alone and in combination with ketamine may increase preexisting IOP in unpremedicated dogs. SpO2 levels below 86.5% may trigger an increase in IOP. Administering KP in a 1:2 ratio at an infusion rate of 0.6 mg/kg/min does not significantly alter IOP for under 45 min in unpremedicated dogs with sufficient oxygenation.

Clinical implications of imprecise sampling time for 10- and 30-min thyrotropin-releasing hormone stimulation tests in horses.

BACKGROUND: The thyrotropin-releasing hormone (TRH) stimulation test is used to diagnose pituitary pars intermedia dysfunction (PPID) using 10- or 30-min protocols. Imprecise sampling time for the 10-min protocol can lead to misdiagnoses. OBJECTIVES: To determine the effect of imprecise sampling time for the 30-min protocol of the TRH stimulation test. STUDY DESIGN: In vivo experiment. METHODS: Plasma immunoreactive adrenocorticotropin (ACTH) concentrations were measured 9, 10, 11, 29, 30 and 31 min after intravenous administration of 1 mg of TRH in 15 control and 12 PPID horses. Differences in ACTH concentrations between sampling times, variability in ACTH concentrations between protocols, and diagnostic classification of PPID were assessed using Friedman's test, Bland-Altman plots, and Fisher's exact test, respectively, with 95% confidence intervals reported and significance set at p < 0.05. RESULTS: Imprecise sampling time resulted in variable ACTH concentrations, but significant differences in absolute ACTH concentrations were not detected for imprecise sampling within each protocol or between protocols. Imprecise sampling changed PPID diagnostic classification for 3/27 (11 [4-28] %) horses for both protocols. Using the 30-min protocol as a reference, 1/12 (8 [1-35] %) horses returned a negative test result and 5/12 (42 [19-68] %) horses returned equivocal test results that would be considered positive in practice due to the presence of supportive clinical signs. MAIN LIMITATIONS: Limited sample size and inter-horse variability reduced the ability to detect small but potentially relevant differences. CONCLUSIONS: Overall, the impact of imprecise sampling was not significantly different between the 10- and 30-min TRH stimulation test protocols. However, diagnostic classification for PPID would have varied between the 10- and 30-min protocols in this population, if clinical signs had been ignored. Precise timing during TRH stimulation tests and contextual interpretation of ACTH concentrations remain fundamental for the diagnosis of PPID.

Pharmacokinetics of hydrorphone hydrochloride after intravenous and subcutaneous administration in ferrets (Mustela putorius furo).

OBJECTIVE: To determine the pharmacokinetic profile of hydromorphone 0.2 mg kg-1 administered by the intravenous (IV) and subcutaneous (SC) route in ferrets. STUDY DESIGN: Randomized, crossover study. ANIMALS: A group of eight adult ferrets weighting (mean ± standard deviation) 1.02 ± 0.22 kg. METHODS: Hydromorphone hydrochloride 0.2 mg kg-1 was administered IV or SC with a washout period of 7 days. Blood samples were collected from a jugular catheter before administration of hydromorphone and at 5, 10, 15, 20, 30, 45, 60, 90, 120, 240, 360, 480 and 720 minutes after hydromorphone administration. Plasma hydromorphone concentrations were determined by liquid chromatography/tandem mass spectrometry. Data were analyzed using a non-linear mixed effects model. RESULTS: The hydromorphone effective half-life was (t1/2) 45 min-1. Systemic clearance (Cls) and the volume of distribution (Vdss) following IV administration were 84.8 mL kg-1 min-1 and 5.59 L kg-1, respectively. The maximum observed plasma concentration was 59.53 ± 14.02 ng mL-1 within 10 minutes following SC administration. The SC bioavailability was 102.0%. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of IV and SC hydromorphone (0.2 mg kg-1) was characterized by a high clearance, short terminal half-life and large volume of distribution. Hydromorphone plasma concentrations remained greater than 2 ng mL-1 for 2 hours in most ferrets, a threshold reported to provide antinociceptive effects in other species. Hydromorphone was well absorbed following SC injection, providing an alternative administration route for clinical use in ferrets.

Pharmacokinetics and bioavailability of meloxicam in Pekin ducks following intravenous, intramuscular and oral administration.

OBJECTIVE: To determine the pharmacokinetics and bioavailability of meloxicam following intravenous (IV), intramuscular (IM), and oral administrations at a dose of 1.0 mg kg-1 in Pekin ducks. STUDY DESIGN: Randomized experimental trial. ANIMALS: A total of 18 clinically healthy male Pekin ducks. METHODS: Pekin ducks were randomly assigned to three groups of six ducks: IV, IM and oral. Meloxicam (1.0 mg kg-1) was administered to each Pekin duck. A non-compartmental analysis was used to evaluate pharmacokinetic parameters. RESULTS: No local or systemic adverse effects were observed in any bird. Meloxicam was detected in the plasma up to 120 hours following IV, IM or oral administration. The elimination half-life of the IV route was slightly shorter than that of the IM and oral routes (p < 0.05). Following IV administration, volume of distribution at steady state and total clearance were 133.17 mL kg-1 and 6.68 mL kg-1 hour-1, respectively. The mean absorption time was 2.29 hours for IM and 1.13 hours for oral route. There were significant differences between IM and oral administration for the peak plasma concentration (Cmax), time to reach Cmax and bioavailability (p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Meloxicam showed long elimination half-life and high bioavailability following IM and oral administration. Meloxicam in Pekin ducks provided the effective therapeutic concentration indicated in other species for up to 48 hours. However, there is a need to determine the clinical efficacy of meloxicam in Pekin ducks.

Evaluation of field-testing protocols to diagnose insulin dysregulation in ponies using a Bayesian approach.

Field tests and their association with laminitis have not been evaluated in large cohorts. The objectives of this study were to evaluate the performance of basal insulin (BI), the oral sugar test (OST) and the insulin tolerance test (ITT) to diagnose ID and investigate their association with laminitis. Insulin dysregulation status was determined in 146 ponies using BI (insulin concentration >20 µIU/mL), an OST (insulin concentration >65 µIU/mL at 60 or 90 min after oral administration of 0.45 mL/kg corn syrup) and an ITT (< 50% reduction in glucose concentration 30 min after intravenous administration of 0.1 IU/kg insulin). Laminitis was identified using modified-Obel scores. A Bayesian approach was used to define the characteristics of the tests and receiver operating characteristic curves were used to assess their association with laminitis. All tests were well tolerated and laminitis was diagnosed in 9% of ponies. Insulin dysregulation was diagnosed in 15% of ponies using BI, 38% using the OST and 54% using the ITT with 11% of ponies positive for all three tests. The sensitivities and specificities of BI, the OST and the ITT to diagnose ID were 0.52 (95% confidence interval [CI], 0.35-0.79) and 0.97 (95% CI, 0.91 - 1.00), 0.84 (95% CI, 0.70 - 0.94) and 0.60 (95% CI, 0.49 - 0.71), and 0.85 (95% CI, 0.68-0.96) and 0.88 (95% CI, 0.75 - 0.97), respectively. Only BI and the OST were associated with laminitis (P = 0.003 and 0.015, respectively).

Age-related changes in the pharmacokinetics of meloxicam after intravenous administration in sheep.

The pharmacokinetics of meloxicam was studied in 1-, 6-, and 12-month-old sheep following a single intravenous (i.v.) dose of 1 mg/kg. The experiments were carried out when the Romanov sheep were 1 month old (7.93 ± 0.91 kg), 6 months old (27.47 ± 4.91 kg), and 12 months old (37.10 ± 3.64 kg). Meloxicam concentration in plasma was determined by high-performance liquid chromatography and the data collected were evaluated by non-compartmental kinetic analysis. Meloxicam was detected in the plasma up to 72 h following i.v. administration in all age groups. The volume of distribution at steady state (Vdss ) and total body clearance (ClT ) were significantly higher in 1-month-old (304.87 mL/kg and 16.57 mL/h/kg) than in 12-month-old (193.43 mL/kg and 10.50 mL/h/kg) sheep. The area under the concentration-time curve from 0 to 72 h value of meloxicam was lower in 1-month-old (58.51 h*µg/mL) compared to 12-month-old (92.59 h*µg/mL) sheep. There was no difference in t1/2ʎz value in different age groups. The body extraction ratio values for meloxicam ranged from 0.0186 to 0.0719 after i.v. administration in all age groups. Meloxicam showed an increase in plasma concentration and a decrease in Vdss and ClT in 12-month-old compared to 1-month-old sheep. Compared to 1-month-old and 12-month-old sheep, there was no difference in these parameters in 6-month-old sheep. Because the age of sheep has an influence on the pharmacokinetics of meloxicam, dosage apparently may need to be adjusted for age.

Oral pharmacokinetics of sulfadiazine and sulfamonomethoxine in female Holstein milking cows.

The efficacy of orally administered drugs in cattle is thought to be slow because of the anatomical and physiological features of their forestomach. Thus, parenteral routes are mainly preferred to administer drugs. However, the effect of some drugs with unique physicochemical properties was promptly obtained even after oral administration in clinically ill cattle. Therefore, the present study aimed to investigate pharmacokinetically the usefulness of the oral route in cattle by comparing the oral pharmacokinetic properties of two sulfonamides with different physicochemical properties. Sulfadiazine (SDZ) and sulfamonomethoxine (SMM) were administered by intravenous and oral route to four female Holstein cows with a 4-weeks washout period. Blood samples were collected over time, and SDZ and SMM concentrations in plasma were analyzed by HPLC. Data obtained from the same animal after intravenous and oral administration were simultaneously analyzed with the one compartment model, and kinetic parameters were calculated. The Tmax (mean ± SD) of SMM (2.75 ± 0.96 hr) was significantly achieved earlier than that of SDZ (5.00 ± 1.15 hr). Further, the mean absorption time of SMM (5.24 ± 0.69 hr) was significantly shorter than that of SDZ (5.92 ± 1.11 hr). Also, the half-life of absorption of SMM (3.91 ± 0.51 hr) was significantly shorter than that of SDZ (4.51 ± 0.82 hr). These data suggest that the absorption rates of highly unionized drugs (such as SMM) from the forestomach of cattle may be markedly higher than less unionized ones (such as SDZ).

Intrathecal mepivacaine after general anesthesia is an effective method of equine euthanasia when compared to intravenous pentobarbital.

OBJECTIVES: This study aims to assess intrathecal mepivacaine for euthanasia in anesthetized horses and compare it to a traditional euthanasia method using a single intravenous injection of pentobarbital in sedated horses. ANIMALS: Client-owned horses and horses requiring euthanasia due to involvement in concurrent research projects were used. Horses were randomly assigned to 1 of 2 groups: intrathecal mepivacaine after anesthesia or intravenous pentobarbital after sedation. All horses had normal vital parameters and no signs of infectious disease at the time of euthanasia. PROCEDURES: The intrathecal mepivacaine group was anesthetized before the intrathecal injection of mepivacaine. The pentobarbital group was sedated, concurrently anesthetized and euthanized using intravenous pentobarbital, then received an intrathecal saline (0.9% NaCl) solution injection to a blind observer. Both groups were sedated with detomidine and the time from sedation to the cessation of vital parameters (respirations, pulse, corneal reflex, and ECG) was recorded. Euthanasias were recorded for review by a blinded anesthesiologist, using an independent scale to assess the quality of sedation, anesthesia induction, and lateral recumbency. RESULTS: Time from detomidine administration to cessation of each vital parameter was significantly longer in the intrathecal mepivacaine group. There was no statistically significant difference in qualitative scores between groups for sedation or induction, but lateral recumbency was subjectively superior in the anesthetized intrathecal mepivacaine group. CLINICAL RELEVANCE: Intrathecal mepivacaine provided a safe, effective, alternative method of euthanasia to intravenous pentobarbital and addresses concerns about barbiturate availability. This study also informs practitioners of what to expect (ie, longer cessation of vital parameters) when using the intrathecal mepivacaine method.

High bioavailability, short half-life, and metabolism into hydromorphone-3-glucuronide following single intramuscular and intravenous administration of hydromorphone hydrochloride to great horned owls (Bubo virginianus).

OBJECTIVE: To determine the pharmacokinetic parameters of hydromorphone hydrochloride and its metabolite, hydromorphone-3-glucuronide (H3G), after a single IV and IM dose in great horned owls (Bubo virginianus). ANIMALS: 6 healthy adult great horned owls (3 females and 3 males). PROCEDURES: A single dose of hydromorphone (0.6 mg/kg) was administered once IM (pectoral muscles) and IV (left jugular) with a 6-week washout period between experiments. Blood samples were collected at 5 minutes and 0.5, 1.5, 2, 3, 6, 9, and 12 hours after drug administration. Plasma hydromorphone and H3G concentrations were determined with liquid chromatography-tandem mass spectrometry, and a noncompartmental analysis was used for the determination of pharmacokinetic parameters. RESULTS: Hydromorphone had a high bioavailability of 170.8 ± 37.6% and rapid elimination after IM administration and rapid plasma clearance and a large volume of distribution after IV administration. Mean Cmax was 225.46 ± 0.2 ng/mL at 13 minutes after IM injection. Mean volume of distribution and plasma drug clearance was 4.29 ± 0.5 L/kg and 62.11 ± 14.6 mL/min/kg, respectively, after IV administration. Mean t1/2 was 1.62 ± 0.36 and 1.35 ± 0.59 hours after IM and IV administration, respectively. The metabolite H3G was readily measured shortly after administration by both routes. CLINICAL RELEVANCE: A single dose of 0.6 mg/kg was well tolerated in all birds. Hydromorphone rapidly attained plasma concentrations following IM administration and had high bioavailability and short t1/2. This study is the first to document the presence of the metabolite H3G in avian species, which suggests similar hydromorphone metabolism as in mammals.

Regional antibiotic perfusion through the lateral saphenous vein in two horses with septic calcaneal osteitis.

In this case report, two horses with chronic refractory infections in the tuber calcanei were successfully managed via intravenous antibiotic regional limb perfusion through the lateral saphenous vein after failure of conventional treatment approaches, including surgery and intravenous regional limb perfusion using the cranial branch of the medial saphenous vein. Surgical delay in these cases may have allowed the development of chronic infection, which prevented the conventional regional perfusion from working effectively. The spatial difference of the vessels relative to the tuber calcanei possibly contributed to the treatment outcome in these horses. This report describes a novel approach for regional antimicrobial perfusion to the equine plantar hock region using the lateral saphenous vein.

Pharmacokinetics of danofloxacin after single oral and intravenous administration in non-laying hens.

The current study aimed to explore the pharmacokinetics of danofloxacin in non-laying hens after a single oral (PO) and intravenous (IV) dose, both at 5 mg/kg body weight (BW). Eighteen 13-week-old healthy hens were equally and randomly divided into two groups. After both doses, blood samples (approximately 1 ml) were collected at different time points. Danofloxacin concentrations were quantified by a validated high-performance liquid chromatography (HPLC) method followed by a non-compartmental analysis using the software of WinNonLin. The elimination half-lives (t1/2λz s) after PO and IV routes were determined as 8.15 ± 3.37 and 7.69 ± 3.40 h, respectively. After IV administration, danofloxacin had an initial concentration (C0 ) of 3.62 µg/ml, a volume of distribution at steady state (VSS ) of 3579.72 ± 454.29 ml/kg, and a total body clearance (Cl) of 0.49 ml/h/g. After PO administration, the absolute bioavailability and absorption half-life (t1/2ka ) were calculated as 100.99% ± 23.10% and 0.82 ± 0.58 h, respectively. Based on the calculated ratio values of AUC/MIC and Cmax /MIC, an oral dose of 5 mg/kg danofloxacin would be expected to successfully treat hens infected with strains with MIC values ≤0.1 µg/ml.

Single oral or intravenous administration of voriconazole achieved recommended therapeutic minimum inhibitory concentrations against Aspergillus in the common raven (Corvus corax).

OBJECTIVE: To determine the pharmacokinetics of voriconazole after single IV or orally administered boluses in common ravens (Corvus corax). ANIMALS: 8 healthy common ravens. PROCEDURES: Voriconazole (5 mg/mL, 10 mg/kg IV) was administered to 8 birds, and then plasma voriconazole concentrations were measured at various time points by high-pressure liquid chromatography with mass spectrometry. Starting 6 months later in a randomized 3-treatment 3-period regimen, birds received a single oral dose of voriconazole suspension (10 mg/mL; 6, 12, and 24 mg/kg PO). The study period was May 2015 to March 2016. RESULTS: Voriconazole (10 mg/kg IV) achieved an initial plasma concentration of 6.31 µg/mL when measured over 21 hours. After oral administration of voriconazole at 6, 12, and 24 mg/kg, the relative bioavailability was 67.5%, 209%, and 183%, respectively. For the 6-mg/kg dose, the maximum plasma concentration was reached at 30 minutes after administration and remained in the therapeutic range of 0.5 to 1 µg/mL for approximately 15 hours. The 12- and 24-mg/kg doses resulted in concentrations in a potentially toxic range. CLINICAL RELEVANCE: Voriconazole was well tolerated. All 4 doses resulted in plasma concentrations of voriconazole > 0.5 µg/mL, which is the minimum inhibitory concentration recommended for pathogenic species of Aspergillus fungi known to affect birds. A single dose of voriconazole administered as 10 mg/kg IV or 6 mg/kg PO resulted in recommended target plasma concentrations. Administration of voriconazole 6 mg/kg PO 2 to 3 times daily may be adequate for treatment without exceeding the toxic range.