Pharmacokinetics of single doses of maropitant citrate in adult horses

The neurokinin‐1 (NK) receptor antagonist, maropitant citrate, mitigates nausea and vomiting in dogs and cats. Nausea is poorly understood and likely under‐recognized in horses. Use of NK‐1 receptor antagonists in horses has not been reported. The purpose of this study was to determine the pharmacokinetic profile of maropitant in seven adult horses after single intravenous (IV; 1 mg/kg) and intragastric (IG; 2 mg/kg) doses. A randomized, crossover design was performed. Serial blood samples were collected after dosing; maropitant concentrations were measured using LC‐MS/MS. Pharmacokinetic parameters were determined using noncompartmental analysis. The mean plasma maropitant concentration 3 min after IV administration was 800 ± 140 ng/ml, elimination half‐life was 10.37 ± 2.07 h, and volume of distribution was 6.54 ± 1.84 L/kg. The maximum concentration following IG administration was 80 ± 40 ng/ml, and elimination half‐life was 9.64 ± 1.27 hr. Oral bioavailability was variable at 13.3 ± 5.3%. Maropitant concentrations achieved after IG administration were comparable to those in small animals. Concentrations after IV administration were lower than in dogs and cats. Elimination half‐life was longer than in dogs and shorter than in cats. This study is the basis for further investigations into using maropitant in horses.     

Anthelmintic efficacy of febantel combined with praziquantel in dogs

Ninety-four dogs were randomly assigned to 1 of 6 groups (5 treated and 1 untreated control) for evaluation of anthelmintic efficacy. Three anthelmintic formulations were studied: a febantel paste, a praziquantel paste, and a combination paste containing both active ingredients. Treated dogs were dosed once daily for 3 days. The minimal effective dosages in combination were established as 10 mg of febantel and 1 mg of praziquantel/kg of body weight. At those dosages for the combination, 99.5% to 100% of the major nematodes and cestodes identified (ie, Ancylostoma caninum, Trichuris vulpis, Toxocara canis, Dipylidium caninum, and Taenia pisiformis) were eliminated. Febantel paste (10 mg/kg) alone was ineffective against cestodes (14.2% elimination of Dipylidium caninum) and praziquantel paste (1 mg/kg) alone was ineffective (0% to 2.4% elimination) against nematodes.     

Evaluation of assays for troponin I in healthy horses and horses with cardiac disease

Cardiac troponin I (cTnI) is a marker for detection of myocardial damage in horses. Many cTnI assays exist and medical studies have shown that the clinical performance of assays differs. The aim of this study was to compare two different cTnI assays in horses. Serum samples were taken from 23 healthy horses (group 1) and 72 horses with cardiac disease (group 2). Cardiac troponin I was determined using assay 1 in laboratory A (limit of detection, LOD, 0.03 ng/mL) and assay 2 in laboratories B and C (LOD 0.01 ng/mL). In group 1, a median cTnI concentration of <0.03 (<0.03–0.04) ng/mL and <0.01 (<0.01–0.15) ng/mL was found with assays 1 and 2, respectively. A higher median value was demonstrated in group 2 for both assays (assay 1: 0.11 ng/mL, range 0.03–58.27 ng/mL, P < 0.001; assay 2: 0.02 ng/mL, range 0.01–22.87 ng/mL, P = 0.044). Although a significant correlation between assays existed, large mean differences that could be important for clinical interpretation of test results were found. A small mean difference was found between laboratories B and C. A significant optimal (P < 0.001) cut-off value for detection of cardiac disease could only be determined for assay 1 (0.035 ng/mL, sensitivity 70%, specificity 91%). Assay 1 performed better for detection of cardiac disease in horses in this study.     

The bioavailability of febantel in dehydrated camels

In the present study the bioavailability of febantel paste and febantel suspension was investigated in the fully hydrated and the dehydrated camel. The serum concentrations of febantel and its metabolites, fenbendazole, oxfendazole and fenbendazole sulfone were determined by high performance liquid chromatography following extraction with ether. The exposure to febantel and its metabolites in fully hydrated camels was significantly higher in camels dosed with febantel paste compared to febantel suspension, as measured by AUC and C _max· The AUC and C _max of fenbendazole and oxfendazole were significantly lower in dehydrated camels as compared to control camels dosed with febantel paste. The systemic availability of febantel suspension in control and dehydrated camels was very low and differences between dehydration and control phases were insignificant. The low systemic availability of febantel in camels dosed with febantel suspension may cause nematodes to become resistant to this anthelmintic. It is, thus, suggested to increase the dose of febantel paste in dehydrated camels in order to increase the exposure to febantel and its metabolites. The binding of febantel, fenbendazole, oxfendazole and fenbendazole sulfone to camels'serum proteins was over 85%. Oxfendazole was only about 70% bound. Dehydration of 10 days did not affect the binding of these benzimidazole derivatives to serum proteins.     

Anthelmintics used in treatment of parasitic infections of horses

The common anthelmintics used to treat parasitic infections of horses are described. Dosage, anthelmintic spectrum, formulation and administration, mode of action, toxicity contraindications, and resistance of parasites to anthelmintics are included.     

Complications associated with cannula insertion techniques used for laparoscopy in standing horses

OBJECTIVE: To report our experience and complications associated with different cannula insertion techniques for laparoscopy in standing horses. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: Forty horses that had laparoscopy for diagnostic or surgical purposes. METHODS: After a physical examination, including rectal palpation, standing laparoscopy was performed in 40 sedated horses. Local anesthetic was injected at each site of cannula insertion in the left flank. Horses were divided into 5 groups: Pneumoperitoneum was induced before cannula insertion using a Verres needle (group 1, n = 3) or a 12-g catheter (group 2, n = 14); the cannula was inserted before inducing a pneumoperitoneum (group 3, n = 9); the cannula was inserted under visual control, using an operating laparoscope (group 4, n = 2) or a Visiport Optical Trocar (group 5, n = 12). Horses were observed for 7 days. RESULTS: Problems with insufflation or cannula insertion occurred in 12 horses: 6 had peritoneal detachment, 4 had a splenic puncture, and 2 had descending colon puncture. Eleven of these complications occurred in groups 1 to 3 and only 1 in groups 4 and 5. CONCLUSIONS: The Visiport optical device allows controlled insertion of the initial trocar, and thus avoided potential problems associated with "blind" cannula insertion techniques and was used effectively in horses that had feed withheld for 12 hours. This technique enables direct insertion of a cannula directly into the right flank. CLINICAL RELEVANCE: Complications associated with initial cannula insertion in the paralumbar fossa, for laparoscopy, in standing horses can be minimized with the use of an optical cannula.     

Evaluation of fenbendazole for treatment of Giardia infection in cats concurrently infected with Cryptosporidium parvum

OBJECTIVE: To determine whether fenbendazole effectively eliminates Giardia organisms from chronically infected cats that have a concurrent Cryptosporidium parvum infection. ANIMALS: 16 clinically normal cats. PROCEDURE: Eight cats with chronic concurrent Giardia and C parvum infections received fenbendazole (50 mg/kg, PO, q 24 h) for 5 days (treatment-group cats). Feces from each cat were collected and processed 3 days weekly for 23 days after treatment. By use of an immunofluorescent assay for detection of Giardia lamblia cysts and C parvum oocysts, organism numbers were counted and scored. Fecal results from treatment-group cats were compared with those of 8 untreated cats with Giardia infection but no C parvum infection (control-group cats). RESULTS: Four of 8 treatment-group cats had consistently negative results for Giardia infection after treatment. These 4 cats had consistently positive results for C parvum oocysts prior to treatment and consistently negative results after treatment. One treatment-group cat had positive results for cysts on all fecal samples, and 3 treatment-group cats had 1 to 3 negative results and then resumed shedding large numbers of cysts; each of these cats had consistently positive results for C parvum oocysts. When compared with control-group cats, treatment-group cats shed less Giardia cysts during week 1 after treatment but not during week 2. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of fenbendazole decreases Giardia cyst shedding to less than detectable numbers in some cats. In our study, persistent C parvum infection may have been associated with failure of fenbendazole to eliminate Giardia infection.     

Pharmacokinetics of maropitant citrate after oral administration of multiple doses in adult horses

The neurokinin-1 (NK-1) receptor antagonist, maropitant citrate, mitigates nausea and vomiting in dogs and cats. Nausea is poorly understood in horses, and clinical use of NK-1 receptor antagonists has not been reported. This study aimed to determine the pharmacokinetics and safety of maropitant after administration of multiple doses. We hypothesized that maropitant concentrations would be similar at steady state to those reported in dogs, with minimal adverse effects. Maropitant was administered at 4 mg/kg orally, once daily for 5 days in seven adult horses. Serial plasma maropitant concentrations were measured by liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic parameters were determined. The maximum, minimum, and average concentrations of maropitant achieved at steady state were 375.5 ± 200, 16.8 ± 7.7, and 73.5 ± 45.1 ng/ml, respectively. The terminal elimination half-life was 11.6 ± 1.4 hr, and the accumulation index was 1.3 ± 0.07. Heart rate decreased between Day 1 and Day 5 (p = .005), with three horses having heart rates of 20 beats per minute and atrioventricular block on Day 5. Pharmacokinetics of repeated maropitant administration suggests the drug could be considered for use in healthy horses. Further investigation on the clinical relevancy of its cardiac effects is warranted.     

Clinical effects of detomidine with or without atropine used for arthrocentesis in horses

The effectiveness of detomidine with or without atropine sulfate premedication in producing sedation and analgesia for arthrocentesis was studied in 12 horses. The effects were evaluated by monitoring heart and respiratory rates, borborygmi, distance from the lower lip to the floor, systolic blood pressure, and response to needle insertion. Either atropine or saline (as a placebo) was administered immediately prior to detomidine. All drugs were administered intravenously. Measurements were taken prior to drug injection and at 1, 5, 10, 15, 20, 25, 30, 40, 50, 60, 120, 180 and 240 minutes postinjection. Detomidine with atropine resulted in significantly higher heart rates than detomidine without atropine for the three hours of observation. Borborygmi were significantly decreased for four hours following detomidine with atropine and for three hours following detomidine without atropine, when compared to preinjection levels. Systolic blood pressure was significantly increased for 15 minutes following detomidine and atropine compared to the preinjection level. The head was markedly lowered for 60 minutes with either treatment. Atropine prevented the bradyarrhythmia and bradycardia induced by detomidine, but it induced a tachycardia. A satisfactory response for needle insertion and adequate synovial fluid aspiration was achieved in 95% of the trials with detomidine, with or without atropine sulfate premedication. The results suggest that, although atropine prevents bradyarrhythmia and bradycardia following detomidine, administering detomidine without atropine is satisfactory for arthrocentesis in untrained horses.     

Evaluation of tear film proteinases in horses with ulcerative keratitis

Ulcerative keratitis is a common and potentially blinding ocular disease of horses, capable of progressing to corneal perforation in as little as 24 h. This rapid stromal degeneration is mediated in part by exogenous and endogenous proteinases. We measured and compared the concentrations of two matrix metalloproteinases (MMP-2 and MMP-9) and a serine proteinase (neutrophil elastase) present in the precorneal tear film of normal horses and horses with rapidly progressing ulcerative keratitis. Precorneal tear film samples were collected from 23 ulcerated and 21 unaffected eyes of 23 horses with unilateral ulcerative keratitis, and from 33 normal eyes of 17 control horses. MMP-2, MMP-9, and neutrophil elastase were identified by casein and gelatin zymography and quantified by computerized image analysis. Median MMP-9 levels were significantly higher in the precorneal tear film of young control horses vs. older control horses ( P  = 0.005). Median MMP-2, MMP-9, and neutrophil elastase levels were significantly higher in the precorneal tear film of ulcerated eyes when compared to age-matched normal controls ( P  = 0.004, P  = 0.001, and P  = 0.012, respectively). Median MMP-2 levels were also significantly higher in the precorneal tear film of contralateral eyes of affected horses when compared to age-matched normal controls ( P  = 0.004). No significant differences in median proteinase levels were detected between 'sterile' ulcers and those from which bacteria or mixed infections (bacteria and fungi) were isolated. However, median MMP-2 and neutrophil elastase levels were significantly higher in the precorneal tear film of eyes with 'sterile' ulcers when compared with ulcerated eyes from which fungi were isolated ( P < 0.05). The results of this study support the use of topical antiproteinase therapy which targets both MMPs and serine proteinases in progressive equine ulcerative keratitis.     

Efficacy and safety of clorsulon used concurrently with ivermectin for control of Fasciola hepatica in Florida beef cattle

The safety and anthelmintic efficacy of clorsulon (7 mg/kg of body weight, orally) given concurrently with ivermectin (0.2 mg/kg, subcutaneously) for control of Fasciola hepatica were evaluated in 75 crossbred beef cattle. Twenty-three control animals were given only ivermectin. Fluke egg counts were significantly lower (P less than 0.0001) in clorsulon-treated animals by day 14 after treatment than before treatment (base line) and were significantly lower (P less than 0.005) after treatment in clorsulon-treated animals than in controls. There was no significant change in fluke egg counts of controls after treatment. The efficacy of clorsulon in reducing F hepatica egg counts was 99%. Clorsulon showed poor efficacy against paramphistomes. Adverse reactions were not observed.     

Evaluation of activated neutrophils in the blood of horses with colic

OBJECTIVE: To evaluate the activation status of neutrophils in blood samples obtained from horses with naturally occurring colic associated with strangulating obstruction, nonstrangulating obstruction, or inflammatory bowel disease. ANIMALS: 30 horses with naturally occurring colic and 30 healthy control horses. PROCEDURE: Activation status of neutrophils was determined by assessing the number of neutrophils that could pass through filters with 5-microm pores, cell-surface CD11-CD18 expression, and alterations in size and granularity of neutrophils. RESULTS: Horses with impaction or gas colic did not have evidence of activated neutrophils. Horses with inflammatory bowel disease consistently had evidence of activated neutrophils, including decreased leukocyte deformability, increased CD11-CD18 expression, increased neutrophil size, and decreased neutrophil granularity. Horses with strangulating colic had variable results. Of horses with strangulating colic, 7 of 14 had marked changes in filtration pressures, 5 of 14 had increased CD11-CD18 expression, 6 of 14 had changes in neutrophil size, and 5 of 14 had changes in neutrophil granularity. Among horses with strangulating colic, changes in deformability, size, and granularity of neutrophils correlated with an adverse outcome. CONCLUSIONS AND CLINICAL RELEVANCE: Activated neutrophils were detected in all horses with inflammatory bowel disease and a few horses with strangulating colic. Correlation of activated neutrophils with horses that had strangulating colic that died or were euthanatized indicates that activated neutrophils are a negative prognostic indicator. Additional studies are needed to determine whether activated neutrophils contribute directly to the adverse outcome in horses with strangulating colic.