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1.
Parasit Vectors ; 17(1): 211, 2024 May 10.
Article En | MEDLINE | ID: mdl-38730429

BACKGROUND: The health and productivity of dairy goats continue to be impacted by gastrointestinal nematodes (GIN) and lungworms (LW). Eprinomectin (EPN) is frequently selected for treatment because it is generally effective and does not require a milk withdrawal period. However, some factors, such as lactation, can have an impact on EPN pharmacokinetics and potentially its efficacy. To evaluate whether this can alter the efficacy of Eprecis® 2%, an eprinomectin injectable solution, a study was performed in lactating goats using the dose currently registered in cattle, sheep and goats (0.2 mg/kg). METHODS: This study was a blinded, randomized, controlled trial performed according to the VICH guidelines. Eighteen (18) worm-free lactating goats were included and experimentally challenged on day 28 with a mixed culture of infective gastrointestinal and lung nematode larvae (Haemonchus contortus, Trichostrongylus colubriformis, Teladorsagia circumcincta, Dictyocaulus filaria). At D-1, fecal samples were collected to confirm patent infection in all animals. On D0, the goats were randomly allocated into two groups of nine goats; group 1 was treated with Eprecis® 2% at 0.2 mg/kg BW by subcutaneous injection, while group 2 remained untreated. Fecal samples for egg counts were collected from all animals on days 3, 5, 7, 9, 11 and 14. On D14, all goats were killed, and the abomasum, small intestine and lungs were removed, processed and subsampled to record the number and species of worms. RESULTS: The treatment was well tolerated. After treatment, the arithmetic mean FEC decreased in the treated group and remained < 5 EPG until the end of the study, while the arithmetic mean FEC in the control group remained > 849.0 EPG. At D14, goats in the treated group had very limited or zero total worm counts, whereas all animals from the control group had a high worm burden. The measured efficacy was 100.0% against H. contortus and T. colubriformis, 99.9% against T. circumcincta and 98.0% against D. filaria. CONCLUSIONS: Eprinomectin (Eprecis®, 20 mg/ml), administered at the label dose (0.2 mg/kg), is highly effective against gastrointestinal nematodes and lungworms in lactating goats.


Feces , Goat Diseases , Goats , Ivermectin , Lactation , Nematode Infections , Animals , Ivermectin/analogs & derivatives , Ivermectin/administration & dosage , Ivermectin/pharmacokinetics , Ivermectin/therapeutic use , Goat Diseases/drug therapy , Goat Diseases/parasitology , Female , Nematode Infections/veterinary , Nematode Infections/drug therapy , Nematode Infections/parasitology , Feces/parasitology , Lactation/drug effects , Parasite Egg Count/veterinary , Injections, Subcutaneous/veterinary , Anthelmintics/administration & dosage , Anthelmintics/therapeutic use , Anthelmintics/pharmacokinetics , Nematoda/drug effects , Gastrointestinal Diseases/veterinary , Gastrointestinal Diseases/parasitology , Gastrointestinal Diseases/drug therapy , Lung/parasitology
3.
Poult Sci ; 103(5): 103571, 2024 May.
Article En | MEDLINE | ID: mdl-38428356

This study aimed to compare the residue depletion of gamithromycin in yellow-feather and white-feather broilers, using Sanhuang and Arbor Acres chickens as typical examples, respectively. Each breed (54 chickens) received a single subcutaneous dose of gamithromycin at 7.5 mg/kg bodyweight (BW). Tissues, including muscle, skin + fat, liver, kidney, and injection site, were collected at 6 h, 3, 5, 7, 10, 14, 21, 28, and 35 d postdrug administration. Gamithromycin concentrations in these tissues were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The kinetics of gamithromycin were analyzed in different tissues using a noncompartmental method in the Phoenix software. Differences were observed in gamithromycin concentrations and kinetic characteristics in both breeds of chickens, with higher residue concentrations and longer residue times found in yellow-feathered broilers. In Sanhuang broilers, the elimination rates of gamithromycin followed this order: injection site > muscle > liver > kidney > skin + fat. The corresponding elimination half-lives (t1/2λzs) in these samples were 1.22, 1.30, 1.71, 2.04, and 2.52 d, respectively. In contrast, in Arbor Acres broilers, a different order was noted: muscle > injection site > kidney > liver > skin + fat, with corresponding t1/2λzs of 1, 1.23, 1.88, 1.93, and 2.21 d, respectively. These differences may be related to variations in pigments in various tissues of chickens of the 2 breeds. However, further investigations are warranted to discern the underlying reasons.


Anti-Bacterial Agents , Chickens , Drug Residues , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/analysis , Drug Residues/analysis , Injections, Subcutaneous/veterinary , Feathers/chemistry , Macrolides/administration & dosage , Macrolides/pharmacokinetics , Macrolides/analysis , Tandem Mass Spectrometry/veterinary , Male
5.
Am J Vet Res ; 85(5)2024 May 01.
Article En | MEDLINE | ID: mdl-38412607

OBJECTIVE: To evaluate and compare the pharmacokinetic parameters of SC ceftazidime administered at 20 and 40 mg/kg to red-eared sliders. ANIMALS: 8 adult red-eared sliders (Trachemys scripta elegans). METHODS: In a sequential, 2-period study with a 3-week washout period between treatments, ceftazidime was administered SC to turtles at 20 and 40 mg/kg. Blood samples were collected from the subcarapacial sinus at 0, 24, 48, 72, 96, and 120 hours after ceftazidime administration. Plasma ceftazidime concentrations were quantified using reversed-phase HPLC. RESULTS: Mean plasma half-life after 20- and 40-mg/kg dosing was 39.75 ± 8.0 hours and 33.03 ± 6.56 hours, respectively. Mean maximum plasma concentration after 20- and 40-mg/kg dosing was 71.0 ± 15.93 µg/mL and 120.0 ± 30.62 µg/mL, respectively. Mean plasma ceftazidime concentrations remained ≥ 8 µg/mL, the theoretical MIC for various reptile pathogens for all time points. CLINICAL RELEVANCE: Results indicate that ceftazidime dosed at either 20 or 40 mg/kg produces plasma concentrations exceeding the theoretical MIC of various reptile pathogens for at least 120 hours. An ideal dosing interval could not be determined, as all plasma concentrations remained above the threshold of interest for all time points. Follow-up studies should focus on establishing a dosing interval and more rigorous monitoring for potential adverse effects.


Anti-Bacterial Agents , Ceftazidime , Turtles , Animals , Turtles/blood , Ceftazidime/pharmacokinetics , Ceftazidime/administration & dosage , Ceftazidime/blood , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/administration & dosage , Injections, Subcutaneous/veterinary , Half-Life , Area Under Curve , Male , Female , Dose-Response Relationship, Drug
6.
J Vet Pharmacol Ther ; 47(2): 87-94, 2024 Mar.
Article En | MEDLINE | ID: mdl-37823356

The benzenedisulfonamide derivative clorsulon is a potent fasciolicide which is marketed in fixed combination injectables, typically combined with the macrocyclic lactone ivermectin. In the presented pharmacokinetic study, the plasma profile of clorsulon in 32 healthy, young Brown Swiss cattle was administered a single intravenous dose at 3 mg/kg body weight or subcutaneously at 3, 6 or 12 mg/kg body weight (4 intact male and 4 female animals per treatment) as a 30% w/v clorsulon injection formulation. Serial blood samples were collected up to 24 days after administration to establish the pharmacokinetics, bioavailability and dose proportionality of clorsulon. Following a single intravenous injection of clorsulon at 3 mg/kg body weight, the area under the concentration versus time curve from the start of dose administration to the time of the last quantifiable concentration (AUClast ) was 4830 ± 941 day*ng/mL, and half-live was 2.37 ± 0.98 days. The back extrapolated concentration at time 0 was 38,500 ± 6070 ng/mL. The volume of distribution at steady state and clearance were 685 ± 107 mL/kg and 664 ± 127 mL/day/kg, respectively. In the groups dosed at 3, 6 or 12 mg/kg body weight by subcutaneous injection, clorsulon plasma concentrations rose to maximum within 0.5 day and decreased to the last sample point. For these groups, the maximum plasma clorsulon concentrations were 3100 ± 838, 5250 ± 1220 and 10,800 ± 1730 ng/mL, respectively, and the AUClast was 5330 ± 925, 9630 ± 1300 and 21,500 ± 3320 day*ng/mL, respectively. Half-lives, 2.01 ± 0.62, 3.84 ± 1.42 and 5.36 ± 0.60 days, respectively, increased significantly with dose, likely related to increasing dose volume. Clorsulon was well absorbed and fully bioavailable (103%-114%) after subcutaneous injection. No gender-related difference in systemic exposure was observed. Assessment of Cmax and AUClast demonstrated a proportional increase in systemic exposure to the clorsulon subcutaneous doses over the range of 3-12 mg/kg body weight.


Ivermectin , Sulfanilamides , Animals , Male , Cattle , Female , Injections, Intravenous/veterinary , Sulfanilamides/therapeutic use , Injections, Subcutaneous/veterinary , Area Under Curve , Body Weight
7.
Vet Anaesth Analg ; 51(2): 152-159, 2024.
Article En | MEDLINE | ID: mdl-38158281

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.


Analgesics, Opioid , Hydromorphone , Animals , Administration, Intravenous/veterinary , Cross-Over Studies , Ferrets , Half-Life , Injections, Intravenous/veterinary , Injections, Subcutaneous/veterinary
8.
Vet Dermatol ; 34(6): 621-623, 2023 Dec.
Article En | MEDLINE | ID: mdl-37743710

This horse presented with subcutaneous mercury panniculitis confirmed by toxicological analysis. Based upon the nature of the lesions the mercury species was elemental mercury (Hg0 ). Despite no history of intentional mercury administration, subcutaneous injection is the presumed most likely route of exposure to Hg0 .


Horse Diseases , Mercury , Male , Animals , Horses , Cellulitis/diagnosis , Cellulitis/veterinary , Belgium , Mercury/toxicity , Mercury/analysis , Injections, Subcutaneous/veterinary
9.
Vet Dermatol ; 34(5): 385-392, 2023 Oct.
Article En | MEDLINE | ID: mdl-37157908

BACKGROUND: The duration of the induction phase of allergen-specific immunotherapy conventionally is a period of several weeks, during which the volume of an allergen solution, administered by injection, is gradually increased until the maintenance dose is reached. In rush immunotherapy (RIT), the induction period is abbreviated to achieve a faster improvement in clinical signs of atopic dermatitis (AD) compared to conventional immunotherapy. OBJECTIVE: The aim of this retrospective study was to evaluate the safety of RIT in 230 dogs with AD and report any adverse effects (AE). ANIMALS: Two hundred thirty client-owned dogs. MATERIALS AND METHODS: Medical records of dogs receiving RIT between 2012 and 2021 were analysed and observed AE were investigated. All dogs underwent RIT following a protocol of subcutaneous allergen extract injections, given hourly with an incrementally increasing volume from 0.1 to 1.0 mL. RESULTS: Adverse effects were documented in 6 of 230 (2.6%) dogs. Five of these dogs (2.2%) showed mild gastrointestinal signs (1 of 5 vomiting, 4 of 5 diarrhoea) and one patient an increase in body temperature by 1.5°C. These occurred at different stages of the RIT protocol. All AE were graded as mild and self-limiting. CONCLUSIONS AND CLINICAL RELEVANCE: Based on these data, supervised RIT in dogs appears to be a safe procedure to achieve the maintenance dose of allergen immunotherapy earlier with infrequent and mild AE.


Dermatitis, Atopic , Dog Diseases , Drug-Related Side Effects and Adverse Reactions , Dogs , Animals , Dermatitis, Atopic/veterinary , Dermatitis, Atopic/drug therapy , Retrospective Studies , Injections, Subcutaneous/veterinary , Immunotherapy/adverse effects , Immunotherapy/veterinary , Immunotherapy/methods , Allergens/adverse effects , Desensitization, Immunologic/adverse effects , Desensitization, Immunologic/veterinary , Desensitization, Immunologic/methods , Drug-Related Side Effects and Adverse Reactions/drug therapy , Drug-Related Side Effects and Adverse Reactions/etiology , Drug-Related Side Effects and Adverse Reactions/veterinary , Dog Diseases/drug therapy
10.
J Vet Pharmacol Ther ; 46(6): 385-392, 2023 Nov.
Article En | MEDLINE | ID: mdl-37246240

The purpose of this study was to assess the pharmacokinetics of robenacoxib (RX), a COX-2 selective non-steroidal anti-inflammatory drug, in goats after single intravenous (IV), subcutaneous (SC) and oral (PO) administrations. 5-month-old healthy female goats (n = 8) were used. The animals were subjected to a three-phase, two-dose (2 mg/kg IV, 4 mg/kg SC, PO) unblinded, parallel study design, with a four-month washout period between the IV and SC treatment, and a one-week period between the SC and PO treatment. Blood was drawn from the jugular vein in heparinized vacutainer tubes at 0, 0.085 (for IV only), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10 and 24 h. Plasma RX concentrations were measured using HPLC coupled to a UV multiple wavelength detector, and the data were pharmacokinetically analysed using ThothPro™ 4.3 software in a non-compartmental approach. Following IV administration, terminal elimination half-life, volume of distribution and total clearance were 0.32 h, 0.24 L/kg and 0.52 L/h/kg, respectively. For SC and PO, the mean peak plasma concentrations were 2.34 and 3.34 µg/mL at 1.50 and 0.50 h, respectively. The t1/2λz was significantly different between the IV and the extravascular (EV) administrations (0.32 h IV vs 1.37 h SC and 1.63 h PO), suggesting the occurrence of a flip-flop phenomenon. The significant difference in Vd values between IV (0.24 L/kg) and EV (0.95 L/kg SC and 1.71 L/kg; corrected for F %) routes might have also triggered the t1/2λz difference. The absolute average SC and PO bioavailability were high (98% and 91%, respectively). In conclusion, the IV administration of RX might not be suitable for goats, due to its short t1/2λz. The EV routes, however, appear to be convenient for the drug's occasional use.


Goats , Female , Animals , Area Under Curve , Injections, Subcutaneous/veterinary , Administration, Oral
11.
J Vet Pharmacol Ther ; 46(3): 177-184, 2023 May.
Article En | MEDLINE | ID: mdl-36633958

Florfenicol was administered to five heifers intramuscularly at a dose rate of 20 mg/kg bwt and following wash-out period, subcutaneously at a dose rate of 40 mg/kg bwt. Blood plasma samples were collected from heifers before injection of florfenicol and up to 120 h after intramuscular (IM) injection and up to 264 h after subcutaneous (SC) injection. Florfenicol concentrations in plasma were measured by high-performance liquid chromatography with mass-spectrometric detection. Pharmacokinetics of florfenicol was estimated using non-compartment analysis. Mean maximum plasma concentration, area under the concentration-time curve and elimination half-life for florfenicol were 3.2 µg/ml, 101.5 µg × h/ml and 24.5 h, respectively, after IM injection at 20 mg/kg bwt, and 2.7 µg/ml, 194.5 µg × h/ml and 103.8 h, respectively, after SC injection at 40 mg/kg bwt. The obtained results indicated that both administration routes provided comparable bioavailability, whereas SC route was attributed with lower peak levels and markedly slower absorption of florfenicol from injection site. Both administration routes provided plasma florfenicol levels which are expected to be effective against prevalent infectious agents of cattle.


Anti-Bacterial Agents , Thiamphenicol , Cattle , Animals , Female , Anti-Bacterial Agents/pharmacokinetics , Thiamphenicol/pharmacokinetics , Injections, Subcutaneous/veterinary , Biological Availability , Injections, Intramuscular/veterinary , Half-Life , Area Under Curve , Injections, Intravenous/veterinary
12.
J Vet Pharmacol Ther ; 45(5): 481-487, 2022 Sep.
Article En | MEDLINE | ID: mdl-35748159

The aim of this study was to determine the pharmacokinetics of carprofen following single and repeated intravenous (IV) administrations at 1.4 and 4 mg/kg doses in sheep. The study was carried out on twelve sheep in two experiments as single- and multiple-dose pharmacokinetics. In experiment 1, carprofen was administered via IV at single doses of 1.4 (n = 6) and 4 mg/kg (n = 6) in a randomized parallel design. In experiment 2, the same dose groups in experiment 1 following the 21-day washout period received intravenously carprofen every 24 h for 5 days. Plasma concentrations were measured using high-performance liquid chromatography-UV and analyzed by a two-compartment open model. After the single administration of 1.4 mg/kg dose, the t1/2α , t1/2el , MRT, ClT , Vdss , and AUC were 0.62 h, 27.57 h, 38.78 h, 2.72 ml/h/kg, 105.26 ml/kg, and 515.12 h*µg/ml, respectively. Carprofen at a single dose of 4 mg/kg showed prolonged t1/2el and MRT, and increased Vdss . On day 5 after the repeated administration of the 1.4 mg/kg dose, the t1/2α , t1/2el , MRT, ClT , Vdss , and AUC were 1.12 h, 57.48 h, 82.18 h, 0.55 ml/h/kg, 45.43 ml/kg, and 2532 h*µg/ml, respectively. Carprofen at a repeated dose of 4 mg/kg showed increased ClT and Vdss and decreased AUC/dose. Although the long t1/2ʎz in single and multiple IV dose studies suggest the possibility of its effective use, the IV route may not be practical in sheep. Therefore, oral and subcutaneous routes of carprofen in sheep would be more valuable in clinical settings.


Carbazoles , Administration, Intravenous/veterinary , Animals , Area Under Curve , Half-Life , Injections, Subcutaneous/veterinary , Sheep
13.
Endocrinology ; 163(2)2022 02 01.
Article En | MEDLINE | ID: mdl-34958103

The specific role of gonadotropin-releasing hormone (GnRH) on brain sexual differentiation remains unclear. To investigate whether gonadotropin and, in turn, testosterone (T) secretion is regulated by GnRH during the critical period for brain differentiation in sheep fetuses, we attempted to selectively suppress pituitary-testicular activation during midgestation with the long-acting GnRH antagonist degarelix. Fetuses received subcutaneous injections of the antagonist or vehicle on day 62 of gestation. After 2 to 3 weeks we examined consequences of the intervention on baseline and GnRH-stimulated plasma luteinizing hormone (LH) and T levels. In addition, we measured the effect of degarelix-treatment on messenger RNA (mRNA) expression for the pituitary gonadotropins and key gonadal steroidogenic enzymes. Baseline and GnRH-stimulated plasma LH levels were significantly suppressed in degarelix-treated male and female fetuses compared to control values. Similarly, T concentrations were suppressed in degarelix-treated males. The percentage of LHß-immunoreactive cells colocalizing c-fos was significantly reduced by degarelix treatment indicating that pituitary sensitivity was inhibited. Degarelix treatment also led to the significant suppression of mRNA expression coding for the pituitary gonadotropin subunits and for the gonadal enzymes involved in androgen synthesis. These findings demonstrate that pharmacologic inhibition of GnRH early in gestation results in suppression of LH secretion and deficits in the plasma T levels of male lamb fetuses. We conclude that GnRH signaling plays a pivotal role for regulating T exposure during the critical period of sheep gestation when the brain is masculinized. Thus, disturbance to gonadotropin secretion during this phase of gestation could have long-term consequence on adult sexual behaviors and fertility.


Gestational Age , Gonadotropin-Releasing Hormone/antagonists & inhibitors , Gonadotropins, Pituitary/metabolism , Oligopeptides/administration & dosage , Pituitary Gland, Anterior/embryology , Sheep/embryology , Animals , Brain/embryology , Female , Fetal Blood/chemistry , Gonadotropin-Releasing Hormone/administration & dosage , Gonadotropin-Releasing Hormone/physiology , Gonadotropins, Pituitary/genetics , Injections, Subcutaneous/veterinary , Luteinizing Hormone/blood , Male , Ovary/chemistry , Ovary/embryology , Pituitary Gland, Anterior/chemistry , Pituitary Gland, Anterior/drug effects , Pregnancy , RNA, Messenger/analysis , Sex Differentiation/physiology , Testis/chemistry , Testis/embryology , Testosterone/blood
14.
Vet Dermatol ; 33(2): 155-e44, 2022 Apr.
Article En | MEDLINE | ID: mdl-34883529

BACKGROUND: Allergen-specific immunotherapy (ASIT) is reported to have a success rate of 50-70% when given for up to 12 months to dogs with atopic dermatitis (AD). How soon ASIT is clinically effective is unclear. OBJECTIVES: To compare the efficacy rate (ER) and time-to-efficacy (TTE) of various types of subcutaneous immunotherapy (SCIT) administered using conventional dosing regimens using the methodology of a critically appraised topic. METHODS AND MATERIALS: Three databases were searched to extract information on the ER and TTE of SCIT in dogs with AD. Herein, "efficacy" was defined as a ≥50% reduction in pruritus and/or skin lesions, and the TTE as the time needed to achieve such a reduction. RESULTS: We selected 12 publications including 194 dogs. The ER was significantly higher with the polymerised allergoids coupled with nonoxidized mannan than for the "classic" aqueous and alum-precipitated SCIT types. A TTE of three months or shorter was seen in a significantly higher proportion of dogs receiving mannan-couple allergoids, pullulan-conjugated Der f 2 or tyrosine-adjuvanted than aqueous or alum-precipitated SCIT; with the latter two formulations, the TTE might be nine months or longer in ≤20% of atopic dogs. CONCLUSIONS AND CLINICAL RELEVANCE: In spite of the low number of articles available for review and small number of enrolled dogs, novel SCIT regimens appear to have a faster - and possibly higher - efficacy than the currently available aqueous or alum-precipitated formulations. A standardisation of outcome measures for ASIT clearly is needed to allow a more meaningful comparison between SCIT types.


Dermatitis, Atopic , Dog Diseases , Allergens , Animals , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/veterinary , Desensitization, Immunologic/methods , Desensitization, Immunologic/veterinary , Dog Diseases/drug therapy , Dogs , Immunotherapy/methods , Immunotherapy/veterinary , Injections, Subcutaneous/veterinary , Pruritus/veterinary
15.
J Vet Pharmacol Ther ; 45(1): 34-45, 2022 Jan.
Article En | MEDLINE | ID: mdl-34622463

Our study objective was to identify a subcutaneous enoxaparin dosage that provided a consistent anticoagulant intensity in dogs. Our hypotheses were that a dose of 0.8 mg/kg would provide inconsistent anticoagulation, a higher dose would provide consistent anticoagulation over a greater duration of time, and viscoelastometry would effectively monitor the anticoagulant status. Six healthy dogs received two subcutaneous enoxaparin doses (0.8 and 2 mg/kg) for anti-Xa activity determinations and pharmacokinetic modeling. Based on calculations derived from these results, 1.3 mg/kg, SC, q8 h was administered for seven doses. Target ranges for anticoagulant intensity were defined as anti-Xa activity of 0.5-1 U/ml, and change from baseline of two viscoelastometric parameters: activated clotting time (ΔACT; ≥40 s), and clot rate (CRpost; ≤20 U/min). Following an initial injection at 1.3 mg/kg, anti-Xa activity of 5/6 dogs reached or exceeded the target range. Following the final dose, anti-Xa activity reached or exceeded the target range in all dogs, and ΔACT and CRpost values exceeded target for 2-6 and 4-12 h, respectively. At an enoxaparin dosage of 1.3 mg/kg, SC, q8 h, anti-Xa activity was consistently above the minimum threshold of the target range; however, the safety of this dosage remains to be determined.


Anticoagulants , Enoxaparin , Animals , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Blood Coagulation , Dogs , Enoxaparin/pharmacology , Injections, Subcutaneous/veterinary
16.
J Vet Intern Med ; 35(6): 2646-2651, 2021 Nov.
Article En | MEDLINE | ID: mdl-34514652

BACKGROUND: Historical and recent literature disagree on whether a higher PO 131 I dosage, compared to IV or SC routes, is required for successful resolution of spontaneous hyperthyroidism in cats, necessitating investigation into the effect of PO and injectable radioactive iodine administration on % thyroidal radioactive iodine uptake (RAIU). HYPOTHESIS/OBJECTIVES: To investigate the effect of PO and SC routes of 123 I administration on paired % thyroidal RAIU in euthyroid cats. Specifically, a 1.5-fold difference (50% relative change) was hypothesized, which in absolute terms can be expressed as a 3.25% increase in the mean %RAIU of 7.04% after PO 123 I administration to 10.56% after SC dosing. ANIMALS: Seven healthy euthyroid teaching-research colony cats. METHODS: A randomized, radiologist-blinded crossover study comparing %RAIU after PO and SC 123 I administration. RESULTS: Percentage thyroidal RAIU values (mean ± SD; 95% confidence interval) after PO (4.81% ± 1.63%; 3.30%-6.23%) and SC (5.26% ± 2.43%; 3.01%-7.51%) 123 I administration were associated with a median within-pair absolute difference of 0.2% (range: min, 0.1%-max, 4.9%). Statistical significance was not achieved (P = .45). Six of 7 cats had a within-pair absolute difference of 0.1% to 0.9% (relative change of 4%-20%), but a single outlier cat had a within-pair absolute difference of 4.9% (relative change of 108%). CONCLUSIONS AND CLINICAL IMPORTANCE: This study did not detect an effect of 123 I administration route on paired % thyroidal RAIU in euthyroid cats. However, a type 2 statistical error due to small sample size is possible.


Cat Diseases , Hyperthyroidism , Iodine , Thyroid Neoplasms , Animals , Cats , Cross-Over Studies , Hyperthyroidism/radiotherapy , Hyperthyroidism/veterinary , Injections, Subcutaneous/veterinary , Iodine Radioisotopes , Thyroid Neoplasms/veterinary
17.
J Vet Pharmacol Ther ; 44(6): 961-966, 2021 Nov.
Article En | MEDLINE | ID: mdl-34427339

Furosemide, a loop diuretic drug, is recommended for use in cases of edema, ascites, congestive heart failure, toxicosis, and acute renal failure in goats. However, its pharmacokinetics and bioavailability have not been reported yet in this species. The aim of this study was to determine the pharmacokinetics and bioavailability of furosemide in goats following intravenous (IV), intramuscular (IM), and subcutaneous (SC) administrations at a dose of 2.5 mg/kg. Six clinically healthy goats received furosemide by each route in a three-way crossover pharmacokinetic design with a 15-day washout period between administrations. The plasma concentrations of furosemide were determined using the high-performance liquid chromatography-UV method and analyzed by non-compartmental analysis. The elimination half-life following IV, IM, and SC administration was 0.71 (0.67-0.76) h, 0.69 (0.61-0.74) h, and 0.70 (0.67-0.79) h, respectively. The volume of distribution at steady state and total clearance for the IV route were 0.17 (0.16-0.19) L/kg and 0.30 (0.27-0.33) L/h/kg, respectively. The peak plasma concentrations of furosemide following IM and SC administrations were 11.19 (10.33-11.95) and 6.49 (5.92-7.00) µg/ml at 0.23 (0.16-0.25) and 0.39 (0.33-0.42) h, respectively. The bioavailability was 109.84 (104.92-116.99)% and 70.80 (55.77-86.67)% for the IM and SC routes, respectively. The pharmacokinetics of furosemide following the IV, IM, and SC administrations in goats demonstrated significant differences, which may have clinical and toxicological implications requiring further investigations.


Furosemide , Goats , Administration, Intravenous/veterinary , Animals , Area Under Curve , Biological Availability , Half-Life , Injections, Intramuscular/veterinary , Injections, Intravenous/veterinary , Injections, Subcutaneous/veterinary
18.
Avian Dis ; 65(2): 310-320, 2021 06.
Article En | MEDLINE | ID: mdl-34412463

In April and November of 2018, multiple commercial laying hen flocks within the same company presented with a sharp increase in mortality and drop in egg production that persisted for several days. These flocks showed striking necropsy lesions consistent with systemic infection and responded to antimicrobial treatment in the feed. Staphylococcus aureus (SA) was the most frequently isolated organism from multiple tissues including comb and wattle lesions, lungs, liver, ovary, spleen, and bone marrow. Given such an uncommon presentation of SA, which is known as a secondary opportunistic pathogen, a challenge study was conducted to evaluate its role in these disease outbreaks. In the present study, laying hens of two ages (22 and 96 wk) were inoculated with SA via three routes: oral gavage, subcutaneous (SC) injection, and intravenous (IV) injection. Both young and old hens in the IV group showed a significant increase in body temperature and drop in body weight; however, the clinical signs observed in the naturally occurring outbreaks were not present. SA was reisolated at multiple time points postchallenge from all challenge groups except the negative control group. While the SC group showed localized necrosis at the injection site, microscopic changes were different from changes observed in birds from the natural outbreaks. Despite observed initial differences in route and age, the SA challenge strain was not capable of reproducing the disease on its own. The results of this study indicate that SA may have played a role in the increased mortality, clinical signs, and necropsy lesions reported with the naturally occurring outbreaks. However, SA should still be considered as a secondary opportunistic pathogen. Other factors that could have caused the initial insult are stress, immunosuppression, or other primary infectious agents. The results of this study may aid veterinary diagnosticians, clinicians, and all poultry professionals to include SA in their differentials list as a secondary opportunistic pathogen in similar cases. This is an uncommon presentation and further field observations and clinical studies are needed to better elucidate the pathogenesis of this disease, which will in turn help to prevent future outbreaks.


Reporte de caso­Comparación de la septicemia por presentación natura o por infección natural por Staphylococcus aureus en gallinas de postura de dos grupos diferentes de edades. En abril y noviembre del 2018, múltiples parvadas comerciales de gallinas de postura dentro de la misma empresa presentaron un marcado aumento en la mortalidad y una caída en la producción de huevo que persistió durante varios días. Estas parvadas mostraron marcadas lesiones a la necropsia compatibles con una infección sistémica y respondieron al tratamiento antimicrobiano en el alimento. El organismo que se aisló con mayor frecuencia de múltiples tejidos fue Staphylococcus aureus (SA), incluyendo lesiones de cresta y barbillas, pulmones, hígado, ovario, bazo y médula ósea. Dada una presentación tan poco común de S. aureus, que se conoce como un patógeno oportunista secundario, se realizó un estudio de desafío para evaluar su papel en estos brotes de enfermedades. En el presente estudio, se inocularon con Staphylococcus aureus gallinas de postura de dos edades (22 y 96 semanas) a través de tres vías: sonda oral, inyección subcutánea (SC) e inyección intravenosa (IV). Tanto las gallinas jóvenes como las de mayor edad del grupo IV mostraron un aumento significativo de la temperatura corporal y una disminución del peso corporal; sin embargo, los signos clínicos observados en los brotes naturales no estaban presentes. Se aisló S. aureus en varios momentos posteriores al desafío de todos los grupos desafiados, excepto el grupo de control negativo. Si bien el grupo inoculado por inyección subcutánea mostraron necrosis localizada en el sitio de la inyección, los cambios microscópicos fueron diferentes de los cambios observados en las aves de los brotes naturales. A pesar de las diferencias iniciales observadas en la ruta y en la edad, la cepa de desafío de S. aureus no fue capaz de reproducir la enfermedad por sí sola. Los resultados de este estudio indican que S. aureus pudo haber jugado un papel en el aumento de la mortalidad, los signos clínicos y las lesiones a la necropsia reportadas con los brotes de origen natural. Sin embargo, se debe considerar S. aureus como un patógeno oportunista secundario. Otros factores que podrían haber causado el daño inicial son el estrés, la inmunosupresión u otros agentes infecciosos primarios. Los resultados de este estudio pueden ayudar a los patólogos veterinarios, clínicos y todos los profesionales avícolas para incluir S. aureus en su lista de diferenciales como patógeno oportunista secundario en casos similares. Esta es una presentación poco común y se necesitan más observaciones de campo y estudios clínicos para dilucidar mejor la patogénesis de esta enfermedad, lo que a su vez ayudará a prevenir futuros brotes.


Chickens , Poultry Diseases/etiology , Sepsis/veterinary , Staphylococcal Infections/veterinary , Administration, Oral , Age Factors , Animal Husbandry/methods , Animals , Autopsy/veterinary , Body Temperature , Body Weight , Bone Marrow/microbiology , Comb and Wattles/microbiology , Comb and Wattles/pathology , Female , Injections, Intravenous/veterinary , Injections, Subcutaneous/veterinary , Liver/pathology , Poultry Diseases/microbiology , Poultry Diseases/pathology , Sepsis/microbiology , Sepsis/pathology , Spleen/microbiology , Staphylococcal Infections/etiology , Staphylococcal Infections/pathology
19.
Vet Res Commun ; 45(4): 181-188, 2021 Dec.
Article En | MEDLINE | ID: mdl-34075527

Three experiments were designed to study the effects of melatonin implantation of ewes and lambs after lambing on the growth of lambs and milk quality throughout lactation. In experiment 1, 53 lambs either did (n = 28) or did not (n = 25) receive a subcutaneous 18-mg melatonin implant at the base of the left ear. In experiment 2, 55 lambs and their mothers either did (lambs: n = 28; ewes: n = 15) or did not (lambs: n = 27; ewes: n = 16) receive a melatonin implant. Milk samples were collected at 15, 30, and 45 d after lambing. In experiment 3, 16 lambs were separated from their mothers 24 h after birth, moved to an artificial rearing unit, and either did (n = 9) or did not (n = 7) receive a melatonin implant. In the three experiments, implants were inserted 24 h after lambing, and lambs were weighed (LW) weekly until weaning (for each experiment, 7, 6, and 5 wk., respectively). Average daily gains (ADG) from birth to weaning were calculated. Melatonin treatment of lambs did not have a significant effect on LW at weaning or ADG, but lambs reared by implanted ewes in experiment 2 presented higher (P < 0.05) LW (±S.E.M.) at weaning (implanted: 13.61 ± 0.51; non-implanted: 12.09 ± 0.57 kg) and ADG (implanted: 221.00 ± 10.45; non-implanted: 189.92 ± 12.44 g/d) than did lambs reared by control ewes. At day 45 of lactation, milk fat and total solid content were higher (P < 0.05) in implanted ewes than they were in control ewes. Groups did not differ significantly in the protein and lactose content of their milk. In conclusion, melatonin treatment of ewes at lambing induced a high growth rate of their lambs and increased the fat content of the milk; however, the direct treatment with melatonin of the lambs at birth did not have an effect in their growth rate.


Ear , Fats/metabolism , Injections, Subcutaneous/veterinary , Melatonin/administration & dosage , Milk/chemistry , Sheep, Domestic , Animal Husbandry , Animals , Female , Lactation , Male
20.
J Vet Pharmacol Ther ; 44(5): 696-704, 2021 Sep.
Article En | MEDLINE | ID: mdl-34080695

Cytosine arabinoside (CA) is a commonly used treatment for dogs with meningoencephalomyelitis of unknown aetiology (MUE) with various proposed protocols, many requiring 24 hours (h) of hospitalization or two visits within 24 h. This is a unidirectional study evaluating the pharmacokinetics of a CA subcutaneous (SC) protocol and a standard constant rate infusion (CRI) protocol in 8 dogs with MUE. Dogs received the CRI (200 mg/m2 IV over 24 h), followed by a SC protocol (50 mg/m2 every 2 h for 4 treatments) four weeks later. Plasma CA concentrations were measured by high-pressure liquid chromatography-tandem mass spectrometry (HPLC-MS). Median peak CA concentration for the SC protocol (3.40 µg/ml, range 1.60-9.70 µg/ml) was significantly higher than the CRI (1.09 µg/ml, range 0.77-1.67 µg/ml; p = .02). Median concentration at 1h and 8h following initiation of treatment was significantly higher for the SC protocol (CA1 2.28 µg/ml, range 0.97-2.67; CA8 1.83 µg/ml, range 0.77-2.84) compared to the CRI (CA1 0.01 µg/ml, range 0-0.45; CA8 0.74 µg/ml, range 0.67-1.11; p = .01). While the PK properties of CA when administered as a CRI has been previously investigated, this study demonstrated that CA when administered via repeated 50 mg/m2 injections every 2 h over an 8-h period, provided sustained plasma levels above its therapeutic target and for a significantly longer duration of time than did a standard CRI protocol.


Dog Diseases , Encephalomyelitis , Animals , Area Under Curve , Cytarabine/therapeutic use , Dog Diseases/drug therapy , Dogs , Encephalomyelitis/drug therapy , Encephalomyelitis/veterinary , Injections, Subcutaneous/veterinary
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