Pharmacokinetics of acetaminophen after a single Oral administration of 20 or 40 mg/kg to 7-9 Day-old foals.

Background: Acetaminophen is utilized in human infants for pain management and fever. Neonatal foals might benefit from administration of acetaminophen but effective and safe dosage regimens for neonatal foals remains to be determined. Objective: The objective was to determine the plasma pharmacokinetics of acetaminophen following oral administration of a single dose of 20 mg/kg or 40 mg/kg to neonatal foals. A secondary objective was to evaluate any changes in hematology and biochemistry profiles. Study design: Randomized study. Methods: Eight clinically healthy 7-9-day old Quarter Horse foals (3 colts and 5 fillies) received a single oral dose of acetaminophen either 20 (n = 4) or 40 (n = 4) mg/kg. Hematology and biochemistry profiles were evaluated before and 7 days after drug administration. Blood samples were collected before and 8 times after acetaminophen administration for 48 h to quantify plasma acetaminophen concentrations. Plasma pharmacokinetic parameters were estimated using non- compartmental analysis. Results: The median peak plasma concentrations (and range) occurred at 1.5 (0.5-2) hours, and 1.0 (1-2) hours for the 20 and 40 mg/kg doses. The maximum plasma concentration (and range) was 12 (7.9-17.4) µg/mL for the 20 mg/kg dose and 14 (11-18) µg/mL for 40 mg/kg dose. The median AUC0-∞ ranged from 46 to 100 and 79 to 160 h*-µg/mL for the 20 and 40 mg/kg dose, respectively. Hematology and biochemistry profiles remained within normal limits. Conclusion: Plasma disposition of acetaminophen after oral administration of 20 and 40 mg/kg to neonates is comparable to adult horses. However, safety and the optimal dosage regimen of acetaminophen for treating pain and or pyrexia in neonates in this age group remains to be determined.

Pharmacokinetics of multiple oral doses of acetaminophen in equine neonates.

OBJECTIVE: To determine the pharmacokinetics and clinical safety of acetaminophen after oral administration of 40 mg/kg q 12 hours or 60 mg/kg q 24 hours for 14 days. ANIMALS: 12 healthy light-breed neonatal foals. PROCEDURES: 6 foals received acetaminophen at 40 mg/kg q 12 hours and 6 foals received 60 mg/kg q 24 hours for 14 days. The study dates were January 31 to April 15, 2023. Physical examinations were performed daily. Plasma disposition of acetaminophen was determined after the first, mid-point drug administration. Hematology and biochemistry analysis was performed before the study, day 7, and the last day of drug administration. Plasma acetaminophen concentrations were determined by high-performance liquid chromatography. Plasma pharmacokinetic parameters were estimated using noncompartmental analysis. RESULTS: No statistically significant changes occurred on hematology or biochemistry profiles. Elevations in γ-glutamyl transferase (GGT) and sorbitol dehydrogenase (SDH) were noted in 4 foals at various time points. The maximum plasma concentration (Cmax) occurred within 2 hours for both doses. The 60 mg/kg dose resulted in a larger median Cmax (range) at 28 µg/mL (22-32) than the 40 mg/kg dose at 23 µg/mL (19-27). The median area under the concentration-vs-time curve from 0 to 8 hours (AUC0-8 hour [range]) was 100 h•µg/mL (82-100) at 40 mg/kg and 128 h•µg/mL (120-168) for 60 mg/kg. Trough concentrations decreased over time for both regimens. CLINICAL RELEVANCE: Foals tolerate oral acetaminophen at 40 mg/kg q 12 hours or 60 mg/kg q 24 hours. Further analgesic and antipyretic studies will help to delineate optimal dosage regimens of acetaminophen to treat foals.

Pharmacokinetics and pharmacodynamics of repeat dosing of gabapentin in adult horses.

BACKGROUND: The repeated administration of high doses of gabapentin may provide better analgesia in horses than current clinical protocols. HYPOTHESIS AND OBJECTIVES: Administration of gabapentin at 40 and 120 mg/kg PO q 12 h for 14 days will not alter serum biochemistry findings or cause adverse effects. Our objectives were to evaluate the effect of gabapentin on serum biochemistry, physical examination, and plasma pharmacokinetics of gabapentin. ANIMALS: Six healthy adult mares. METHODS: Horses received 40 and 120 mg/kg of gabapentin orally q 12 h for 14 days. Horses were examined and scored for ataxia and sedation daily. Serum biochemistry variables were analyzed before treatment and days 7 and 14 after gabapentin administration. Plasma disposition of gabapentin was evaluated after the first and last drug administration. Pharmacokinetic parameters were estimated using noncompartmental analysis. RESULTS: No changes occurred in physiologic or biochemical variables. Median (range) maximal plasma gabapentin concentrations (µg/mL) after the last dose (day 15) were 7.6 (6.2-11) and 22 (14-33) for 40 mg/kg and 120 mg/kg doses respectively. Maximal concentration of gabapentin was reached within 1 hour after drug administration. Repeated administration of gabapentin resulted in a median (range) area under the curve (AUC0-12 hours ) last/first dose ratio of 1.5 (1.00-2.63) and 2.92 (1.4-3.8) for the 40 and 120 mg/kg regimens, respectively. CONCLUSION AND CLINICAL IMPORTANCE: Our results suggest that horses tolerate gabapentin up to 120 mg/kg PO q 12 h for 14 days. The analgesic effect of the dosage regimens evaluated in our study warrants further research.

Validation of a Rapid Bronchoalveolar Lavage Fluid Colorimetric Evaluation for Assessing the Severity of Exercise-Induced Pulmonary Hemorrhage in Horses in Field Conditions.

Diagnosis and assessment of severity of exercise-induced pulmonary hemorrhage (EIPH) relies on postexercise visualization of fresh blood in the airways via tracheobronchoscopic examination (TBE) and/or counting erythrocytes in bronchoalveolar lavage fluid (BALFRBC). Determining the BALFRBC is more sensitive than TBE but its usefulness is hampered by the need to have BALFRBC counted at a laboratory. We explored the feasibility of evaluating the severity of EIPH by using a color chart comprised of five shades of red and matching those colors with the color of BALF immediately following collection. To validate the technique, sets of ten BALF samples with known BALFRBC numbers were created and randomly shown to two groups of 18 observers who independently matched the color of the BALF with one of the shades of red displayed on the screen of a smartphone. Interobserver and intra-observer agreements regarding colors were > 0.9. The utility of the color chart was further validated under field conditions at two barrel racing events where 63 BALF samples were collected from 21 horses and BALF color was graded independently by three observers. The number of BALFRBC in the 63 samples ranged from 25-1,100,000/µL. EIPH was diagnosed in 39 samples based on the detection of color, and all 5 colors were matched multiple times with BALF samples. Overall, the color of the BALF was related to the number of BALFRBC. Colorimetric evaluation of BALF represents a practical and reliable option for rapid postexercise assessment of the presence and severity of EIPH.

Plasma disposition of gabapentin after the intragastric administration of escalating doses to adult horses.

BACKGROUND: In humans, gabapentin an analgesic, undergoes non-proportional pharmacokinetics which can alter efficacy. No information exists on the pharmacokinetics of dosages >20 mg/kg, escalating dosages or dose proportionality of gabapentin in horses. HYPOTHESIS AND OBJECTIVES: Gabapentin exposure in plasma would not increase proportionally relative to the dose in horses receiving dosages ≥20 mg/kg. To assess the plasma pharmacokinetics of gabapentin after nasogastric administration of gabapentin at dosages of 10 to 160 mg/kg in adult horses. ANIMALS: Nine clinically healthy adult Arabian and Quarter Horses. METHODS: In a randomized blinded trial, gabapentin was administered by nasogastric intubation to horses at 10, 20 mg/kg (n = 3) and 60, 80, 120, 160 mg/kg (n = 6). Plasma was collected before and at regular times over 64 hours after administration of gabapentin. Gabapentin was quantified using a validated chromatographic method. Dose proportionality was estimated using a power model. Pharmacokinetic parameters were estimated using compartmental pharmacokinetic analysis. RESULTS: Plasma pharmacokinetics parameters of gabapentin were estimated after nasogastric administration at dosages of 10 to 160 mg/kg. Gabapentin plasma concentration increased with dose increments. However, the area under the concentration curve from zero to infinity and maximal plasma concentration did not increase proportionally relative to the dose in horses. CONCLUSIONS AND CLINICAL IMPORTANCE: Gabapentin exposure in plasma is not proportional relative to the dose in horses receiving nasogastric dosages of 10 to 160 mg/kg.

Relationship between tracheobronchoscopic score and bronchoalveolar lavage red blood cell numbers in the diagnosis of exercise-induced pulmonary hemorrhage in horses.

BACKGROUND: Exercise-induced pulmonary hemorrhage (EIPH) is diagnosed and its severity assessed by post-exercise tracheobronchoscopy, and enumeration of bronchoalveolar lavage fluid red blood cells (BALFRBC). Minimal information is available regarding the relationship of tracheobronchoscopy score to BALFRBC number. OBJECTIVE: Evaluate the relationship between BALFRBC number and tracheobronchoscopy scores and determine their diagnostic sensitivities. ANIMALS: Nine sedentary horses, 21 fit Thoroughbreds, 129 Barrel Racers. METHODS: Normal BALFRBC number and the effect of bronchoalveolar lavage (BAL) on it were evaluated by performing 2 BALs 24 hours apart in sedentary horses. Tracheobronchoscopy followed by BAL was performed 247 times on 150 horses after treadmill, racetrack, or barrel racing exercise. Lastly, a BALFRBC diagnostic threshold number that optimized the geometric mean of the sensitivity and precision (F1-score) was determined using Bayesian analysis. RESULTS: No increase in BALFRBC occurred after the second BAL (mean ± SD, 304 ± 173/µL). Tracheobronchoscopy scores ranged from 0 (n = 112) to 4 (n = 4) and BALFRBC ranged from 102 to 4605268/µL. Spearman correlation between tracheobronchoscopy score and BALFRBC was weak (P < .001; rs = 0.42) with large ranges of BALFRBC associated with each tracheobronchoscopy score. The highest F1-score occurred for a BALFRBC threshold number = 992/µL. Seventy-five tracheobronchoscopy scores equaled 0 although BALFRBC number was ≥992/µL. Sensitivity of tracheobronchoscopy for diagnosing EIPH was poor (0.59; 95% confidence intervals [CI], 0.49-0.68), compared to BALFRBC number ≥992/µL (0.93; 95% CI, 0.88-0.96). CONCLUSIONS AND CLINICAL IMPORTANCE: False negatives are common with tracheobronchoscopy. Follow-up determination of BALFRBC may be indicated for tracheobronchoscopy scores = 0 before EIPH can be ruled out.

Evaluation of equine coronavirus fecal shedding among hospitalized horses.

BACKGROUND: Currently, diagnosis of equine coronavirus (ECoV) relies on the exclusion of other infectious causes of enteric disease along with molecular detection of ECoV in feces or tissue. Although this approach is complete, it is costly and may not always be achievable. OBJECTIVE: We hypothesized that the overall fecal shedding of ECoV in hospitalized horses is low. Our objective was to determine whether systemically healthy horses and horses with gastrointestinal disorders shed ECoV in their feces at the time of admission to a referral hospital and after 48 hours of stress associated with hospitalization. ANIMALS: One-hundred thirty adult horses admitted to the Washington State University Veterinary Teaching Hospital for gastrointestinal disease (n = 65) or for imaging under anesthesia (n = 65) that were hospitalized for 48 hours. Owner consent was obtained before sampling. METHODS: Fecal samples were collected at admission and 48 hours later. Polymerase chain reaction (PCR) for ECoV and electron microscopy (EM) were performed on all samples. RESULTS: Only 1 of 258 fecal samples was PCR-positive for ECoV. Electron microscopy identified ECoV-like particles in 9 of 258 samples, parvovirus-like particles in 4 of 258 samples, and rotavirus-like particles in 1 of 258 samples. CONCLUSIONS AND CLINICAL IMPORTANCE: The presence of ECoV in feces of hospitalized adult horses was low. Thus, fecal samples that are PCR-positive for ECoV in adult horses that have clinical signs consistent with this viral infection are likely to be of diagnostic relevance. The clinical relevance of the viruses observed using EM remains to be investigated.

Exercise-induced pulmonary hemorrhage in barrel racing horses in the Pacific Northwest region of the United States.

BACKGROUND: Exercise-induced pulmonary hemorrhage (EIPH) refers to bleeding from the lungs in association with strenuous exercise. It has been documented in race horses but little information exists on EIPH in barrel racing horses. HYPOTHESIS/OBJECTIVES: Our goals were to evaluate the presence of EIPH in barrel racing horses and estimate its prevalence in the Pacific Northwest. ANIMALS: 149 barrel racing horses enrolled at events in WA (11), ID (3), and MT (33). METHODS: Observational cross-sectional study. Data collected included signalment, history of illness, respiratory disease, race division, and pre-race medications. Endoscopy was performed and tracheobronchoscopic (TBE) EIPH score was assigned based on quantity of blood in the trachea (0 = no blood to 4 = abundance of blood within the trachea). After TBE, bronchoalveolar lavage (BAL) was performed. Erythrocyte (red blood cell, RBC) counts were obtained from bronchoalveolar lavage fluid (BALF). Statistical analysis included linear and logistic regression, Fisher's exact t test, and calculation of correlation coefficient. Significance was set at P < .05. RESULTS: The prevalence of EIPH based on TBE EIPH score was 54%. When based on BALF RBC count >1,000 cells, EIPH prevalence was 66%. Race time did not significantly affect the presence of EIPH. A significant (P < .0001) positive linear relationship between the TBE and BAL erythrocyte count was identified, but its strength was poor (r2 = .15). CONCLUSIONS AND CLINICAL IMPORTANCE: EIPH occurs in over 50% of barrel racing horses in the Pacific Northwest. Precise determination of the impact of EIPH on health of barrel racers requires further study.

The Effects of Mepivacaine Hydrochloride on Antimicrobial Activity and Mechanical Nociceptive Threshold During Amikacin Sulfate Regional Limb Perfusion in the Horse.

OBJECTIVE: To determine the effect of intravenous regional limb perfusion (IVRLP) with a combination of mepivacaine hydrochloride and amikacin sulfate on synovial fluid amikacin sulfate concentration, antimicrobial activity, and mechanical nociceptive threshold (MNT). STUDY DESIGN: Experimental study. ANIMALS: Healthy adult horses (n=9). METHODS: One IVRLP treatment was randomly administered by cephalic vein of each limb: amikacin alone (1 g amikacin in 60 mL saline) or amikacin with mepivacaine (1 g amikacin and 500 mg mepivacaine in 60 mL saline). Opposite treatments were repeated after a 24 hour wash-out period. Amikacin concentration and antimicrobial activity were determined for synovial fluid from middle carpal joints at tourniquet removal and 30 minutes following. Zone of inhibition was determined for Staphylococcus aureus and Escherichia coli. MNT was determined at 3 dorsal metacarpal locations prior to and after sedation, after Esmarch tourniquet application, and 30 minutes after IVRLP prior to and after tourniquet removal. RESULTS: Two limbs from each treatment group were removed because of undetectable amikacin concentrations for a total of 14 data sets analyzed. Synovial fluid amikacin concentrations and zone of inhibition were not significantly different between treatments at any time point. MNT were significantly increased 30 minutes after IVRLP prior to and following tourniquet removal using amikacin and mepivacaine (median, range; 40.0 µg/mL, 38.7-40.0 and 40.0, 25.8-40.0, respectively) compared to amikacin alone (19.5 µg/mL, 18.7-25.6 and 15.3, 13.2-20.5, respectively). CONCLUSION: Addition of mepivacaine to amikacin for IVRLP in the horse as a means of providing analgesia without decreasing antimicrobial activity.

Camelid heat stress: 15 cases (2003-2011).

This case series describes novel findings associated with heat stress in 15 cases in South American camelids that had no pre-existing illnesses and which had clinical signs of illness after exposure to a warm environment. Novel findings include decreased packed cell volume and albumin concentration and mild spinal axonal degeneration. Heat stress should be considered in weak camelids with a history of hyperthermia.

Stress thermique chez les camélidés : 15 cas (2003­2011). Cette série de cas décrit des constatations nouvelles associées au stress thermique dans 15 cas chez des camélidés d'Amérique du Sud qui n'avaient aucune maladie préexistante et qui ont présenté des signes de maladie après l'exposition à un environnement chaud. Les constatations nouvelles comprennent une valeur d'hématocrite réduite et une concentration d'albumine et une légère dégénération rachidienne axonale. Le stress thermique devrait être considéré chez les camélidés affaiblis ayant des antécédents d'hyperthermie.(Traduit par Isabelle Vallières).

Corynebacterium pseudotuberculosis liver abscess in a mature alpaca (Lama pacos).

A mature female alpaca was evaluated for weight loss and a 10-day history of anorexia, diarrhea, abdominal distension, and ventral edema. Ultrasonography revealed a hepatic mass, culture of which identified Corynebacterium pseudotuberculosis. This is the first reported case of an internal caseous lymphadenitis lesion resulting in clinical disease in a camelid.

What is your diagnosis? Biopsy impression smear of a hepatic mass in a yearling Thoroughbred filly.

A 1-year-old Thoroughbred filly was presented to the Cornell University Hospital for Animals with a 10-day history of fever, diarrhea, inappetance, and hypodipsia. Clinical pathology abnormalities found by the referring veterinarian included erythrocytosis, hyperproteinemia, and increased serum gamma-glutamyltransferase and lactate dehydrogenase activities. At Cornell University, the laboratory abnormalities were confirmed and also included thrombocytosis and hypoglycemia. Erythrocytosis persisted despite vigorous fluid therapy. Ultrasound examination revealed an extremely enlarged liver with abnormal echogenicity and a 21 x 25-cm hepatic mass with varied echogenicity. Imprints of an ultrasound-guided biopsy of the mass revealed a neoplastic epithelial population of uncertain origin, although the cells did not resemble hepatocytes. Together with the presenting signs, signalment, ultrasonographic findings, and persistent erythrocytosis, the cytologic findings were considered to be most consistent with hepatoblastoma. Histopathologic examination of the mass at necropsy confirmed the diagnosis and findings also included bone marrow erythroid hyperplasia. Serum erythropoietin concentration was 28.0 mU/mL (reference interval 1.0-11.8 mU/mL), supporting erythropoietin production by the tumor and secondary inappropriate erythrocytosis. To our knowledge, this report is the first to document secondary erythrocytosis with increased erythropoietin concentration in a horse with hepatoblastoma, and also the first to describe the cytopathologic features of this rare tumor.

Cytokine profiles of peripheral blood mononuclear cells isolated from septic and healthy neonatal foals.

BACKGROUND: Septicemia initiates the production of pro-inflammatory (interleukin [IL] 1-beta [IL-1beta], interferon-gamma [IFN-gamma], IL-6), and anti-inflammatory (IL-4) cytokines. The transcription of some of these proteins (IL-8, IL-6) is linked to endotoxin-induced activation of the toll-like receptor 4 (TLR4) on peripheral blood mononuclear cells (PBMC). HYPOTHESES: Septic foals fail to increase gene expression of IFN-gamma. Nonsurviving septic foals exhibit distinctive cytokine profiles. ANIMALS: Twenty-one septic and 20 healthy neonatal foals. METHODS: Using real-time polymerase chain reaction, gene expression of IFN-gamma, IL-1beta, IL-6, IL-4, IL-8, TLR4, and beta-actin in PBMC were measured in samples obtained from septic foals at 0, 24, and 72 hours (T = 0, 24, and 72 hours) after admission to the Cornell University Hospital for Animals. Control foals were sampled at comparable times. RESULTS: At T=0 hours, septic foals exhibited a 6-fold decrease in gene expression of IL-4 and a 5-fold increase in gene expression of TLR4. Gene expression of IFN-gamma, IL-6, IL-8, or of IL-1beta did not differ between the 2 groups of foals at T = 0 hours. In septic foals that died (n = 3), there was a 15-fold increase in IL-6 at T = 0 hours compared to survivors. CONCLUSIONS AND CLINICAL IMPORTANCE: Septic foals, unlike septic human infants, up-regulate TLR4 gene expression, which may enhance pro-inflammatory cytokine production. Despite the presence of sepsis, IFN-gamma was not up-regulated. Additional studies are needed to verify that increased IL-6 expression is associated with a poor prognosis in septic foals.

Assessment of serum concentrations and sedative effects of fentanyl after transdermal administration at three dosages in healthy llamas.

OBJECTIVE: To determine the serum concentrations and sedative effects of fentanyl after transdermal administration at 3 dosages in llamas. ANIMALS: 9 healthy adult female llamas (mean age, 8 +/- 3 years; mean weight, 150 +/- 18 kg). PROCEDURE: Llamas were allocated to 1 of 3 groups (3 llamas/group). Fentanyl patches (each providing transdermal delivery of 75 microg of fentanyl/h) were placed on shaved areas of the antebrachium of all llamas. In group 1, llamas were treated with 1 patch (anticipated fentanyl dosage, 75 microg/h). In group 2, llamas were treated with 2 patches (anticipated fentanyl dosage, 150 microg/h). In group 3, llamas were treated with 4 patches (anticipated fentanyl dosage, 300 microg/h). For each llama, the degree of sedation was assessed by use of a subjective scoring system and a blood sample was collected for determination of serum fentanyl concentration at 12, 24, 36, 48, 60, and 72 hours after patch placement. RESULTS: Following the placement of 4 patches, mean +/- SD serum fentanyl concentration in group 3 llamas reached 0.3 +/- 0.08 ng/mL within 12 hours. This concentration was sustained for 72 hours. In group 2, application of 2 patches provided inconsistent results; in group 1, application of 1 patch rarely provided measurable serum fentanyl concentrations. No llamas became sedated at any time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that application of four 75 microg/h fentanyl patches provides consistent, sustained serum fentanyl concentrations without sedation in llamas. However, the serum concentration of fentanyl that provides analgesia in llamas is not known.