Evaluation of doramectin for the treatment of experimental canine spirocercosis

The nematode Spirocerca lupi is primarily a parasite of dogs, which causes typical lesions of esophageal nodular granulomas, aortic aneurysms and spondylitis. In order to evaluate the therapeutic effect of doramectin on experimental canine spirocercosis, seven beagle dogs experimentally infected with 40 infectious S. lupi larvae (L(3)) were treated with doramectin. Treatment was commenced following endoscopic visualization of esophageal granulomas, and typical S. lupi eggs were detected in the feces. The treatment protocol included six treatments of doramectin (400 microg/kg subcutaneously) at 2 weeks intervals, followed by monthly injections until the disappearance of the esophageal granulomas or the end of the study (768 days post-inoculation).Eggs could not be found on fecal examinations 3-10 days after the first or second doramectin treatment. In addition, a gradual decrease in size of granulomas was noticed in all seven dogs during the course of the study. Esophageal granulomas had completely resolved in six of the seven dogs between day 35 and day 544 post-initial doramectin treatment, by day 35 in one dog (after three treatments), by day 43 in two dogs (after four treatments), by day 98 in one dog (after seven treatments), by day 460 in one dog (after 18 treatments) and by day 544 in another dog (after 21 treatments). In one dog, remnants of S. lupi granulomas could still be seen 544 days post-initiation of treatment with doramectin. Multiple subcutaneous injections of doramectin (400 microg/kg) were shown to be effective and safe in the treatment of canine spirocercosis.     

Spirocerca lupi esophageal granulomas in 7 dogs: resolution after treatment with doramectin

Seven dogs with Spirocerca lupi esophageal granulomas were identified based on the site of involvement (ie, distal esophagus) and characteristic endoscopic appearance. Six dogs presented with signs of esophageal disease and 1 dog was asymptomatic. Ova were only identified in the feces of 2 dogs. On thoracic radiographs, 4 dogs had evidence of a caudodorsal mediastinal mass, and 2 of these dogs had spondylitis of midthoracic vertebrae. On endoscopy, single esophageal nodules were observed in 5 dogs, 1 dog had 3 nodules, and 1 dog had 6 nodules. All 7 dogs were treated with doramectin at a dosage of 200 microg/kg SC at 14-day intervals for 3 treatments. Dogs had physical and endoscopic examinations at 2, 4, and 6 weeks after treatment. By 6 weeks, clinical signs had resolved in 6 dogs (1 dog was asymptomatic), and the esophageal nodules had completely resolved in 4 dogs, and incompletely resolved in 3 dogs. Two dogs with incomplete resolution were treated again with doramectin at 500 microg/kg PO daily for an additional 6 weeks. Complete resolution of the esophageal nodules was confirmed by endoscopy in all dogs. Nodules had resolved in 4 dogs by 6 weeks, in 2 dogs by 12 weeks (after 6 weeks additional daily oral therapy), and in 1 dog 22 months after the initial 200 microg/kg treatment regimen. No dog experienced adverse effects to the drug, and all symptomatic dogs have been free of disease for periods ranging from 3 to 4 years.     

Comparative plasma dispositions of ivermectin and doramectin following subcutaneous and oral administration in dogs

This study evaluates the comparative plasma dispositions of ivermectin (IVM) and doramectin (DRM) following oral and subcutaneous administration (200 microg/kg) over a 40-day period in dogs. Twenty bitches were allocated by weight in to four groups (Groups I-IV) of five animals each. Animals in the first two groups (Groups I and II) received orally the injectable solutions of IVM and DRM, respectively, at the dose of 200 microg/kg bodyweight. The other two groups (Groups III and IV) received subcutaneously injectable solutions at the same dose rate. Blood samples were collected between 1h and 40 days after treatment and the plasma samples were analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The results indicated that IVM produced a significantly higher maximum plasma concentration (C(max): 116.80+/-10.79 ng/ml) with slower absorption (t(max): 0.23+/-0.09 day) and larger area under the concentration versus time curve (AUC: 236.79+/-41.45 ng day/ml) as compared with DRM (C(max): 86.47+/-19.80 ng/ml, t(max): 0.12+/-0.05 day, AUC: 183.48+/-13.17 ng day/ml) following oral administration of both drugs; whereas no significant differences were observed on the pharmacokinetic parameters between IVM and DRM after subcutaneous administrations. In addition, subcutaneously given IVM and DRM presented a significantly lower maximum plasma concentration (C(max): 66.80+/-9.67 ng/ml and 54.78+/-11.99 ng/ml, respectively) with slower absorption (t(max): 1.40+/-1.00 day and 1.70+/-0.76 day, respectively) and larger area under the concentration versus time curve (AUC: 349.18+/-47.79 ng day/ml and 292.10+/-78.76 ng day/ml, respectively) as compared with the oral administration of IVM and DRM, respectively. No difference was observed for the terminal half-lives ((t(1/2lambda(z)) and mean residence times (MRT) of both molecules. Considering the pharmacokinetic parameters, IVM and DRM could be used by the oral or subcutaneous route for the control of parasitic infection in dogs.     

Successful transendoscopic oesophageal mass ablation in two dogs with Spirocerca lupi associated oesophageal sarcoma

This report describes two cases of oesophageal tumours managed by transendoscopic neodymium:yttrium‐aluminum‐garnet laser ablation and polypectomy snare electrocautery. In each dog oesophagoscopy revealed caudal oesophageal masses, suspected to be Spirocerca lupi‐induced oesophageal neoplasia. To resect the masses, transendoscopic neodymium:yttrium‐aluminum‐garnet laser ablation was used in the first case and polypectomy snare electrocautery in the second. Recovery was uneventful. Histopathology was consistent with oesophageal fibrosarcoma and osteosarcoma in each case, respectively. Follow‐up oesophagoscopy revealed apparently healthy oesophageal tissue except for focal scar tissue in the first case. Transendoscopic laser ablation and polypectomy snare electrocautery is a potential non‐invasive, cost effective alternative for surgical oesophageal mass resection.     

Successful resolution of dermatophyte mycetoma following terbinafine treatment in two cats

Microsporum canis sensitive to itraconazole and terbinafine was isolated from two cats presented with generalized dermatophytosis and dermatophyte mycetoma. Itraconazole therapy was withdrawn through lack of efficacy in one cat (a Persian) and unacceptable adverse effects in the other (a Maine Coon). Both cats achieved clinical and mycological cure after 12–14 weeks therapy with 26–31 mg kg^?1 terbinafine every 24 h per os (PO). Clinical signs in the Maine Coon resolved completely after 7 weeks treatment. Four weeks of therapy with additional weekly washes with a 2% chlorhexidine/2% miconazole shampoo following clipping produced a 98% reduction in the Persian cat's mycetoma, which was then surgically excised. Recurrent generalized dermatophytosis in the Persian cat has been managed with pulse therapy with 26 mg kg^?1 terbinafine every 24 h PO for 1 week in every month. No underlying conditions predisposing to dermatophytosis were found in either cat despite extensive investigation. Terbinafine administration was associated with mild to moderate lethargy in the Persian cat, but no other adverse effects or changes in blood parameters were seen. To the best of the authors’ knowledge this is the first report of a dermatophyte mycetoma in a Maine Coon and of successful resolution of this condition in cats following terbinafine therapy.     

Successful treatment of traumatic oesophageal rupture with severe cellulitis in a mare

A five-year-old standardbred mare suffered a cervical oesophageal rupture subsequent to a kick. Marked cellulitis and extensive soft tissue damage resulted. Treatment consisted of creating an oesophageal fistula, local debridement and systemic antibiotics. The mare made a long but successful recovery. Treatment of oesophageal rupture in the horse is discussed.     

Successful medical treatment of 15 dogs with pyothorax

OBJECTIVES: To review the success of non-surgical management, which included antibiotics and a single thoracocentesis, in 15 dogs presenting with pyothorax. METHODS: Sixteen dogs were selected retrospectively from case files at the Veterinary Cardiorespiratory Centre. RESULTS: One dog was diagnosed with a mass suspected to be a pulmonary abscess on ultrasound examination and was referred for surgery. Fifteen dogs were treated medically. Springer spaniels were the most commonly presented breed (six cases) followed by Labrador retrievers (three cases). Under sedation or general anaesthesia, thoracocentesis was performed unilaterally and as much purulent effusion as possible was removed. Lavage of the thorax was not undertaken. In most dogs, antibiotic treatment was ampicillin at a mean dose of 33 mg/kg administered three times daily and 25 mg/kg metronidazole administered twice daily. Antibiotics were provided for a minimum of six weeks. All dogs recovered completely and did not show relapse on prolonged follow-up. This included one dog, which had very widespread pleural adhesions and minimal effusion. CLINICAL SIGNIFICANCE: In dogs that do not have evidence of pulmonary masses or consolidations and no evidence of granular pleural effusion, medical therapy may be curative even in chronic cases of pyothorax with pleural adhesions.     

Use of adjuvant carboplatin for treatment of dogs with oral malignant melanoma following surgical excision

Melanoma is the most common oral malignancy in dogs. This retrospective study evaluated adjuvant carboplatin chemotherapy (with or without radiation therapy) in 17 dogs with malignant oral melanoma following surgical resection. The median dosage and number of doses of carboplatin administered to the 17 dogs was 300 mg m^?2 (range, 150–300 mg m^?2) and 4 (range, 2–11), respectively. The overall median progression‐free survival for all dogs was 259 days [95% confidence interval (CI₉₅), 119–399 days]. The first progression‐free survival event was local recurrence in seven dogs (41%) and metastases in seven dogs (41%). The median overall survival for all dogs was 440 days (CI₉₅, 247–633 days). The tumour was the cause of death in 10 dogs (59%). On the basis of this study, systemic therapy with carboplatin may be an appropriate adjunct to local treatment for canine malignant melanoma, although future prospective controlled studies are needed to compare treatment modalities for this aggressive neoplasia.     

Acute aortic rupture in a dog with spirocercosis following the administration of medetomidine

Spirocercosis is an emerging disease in veterinary medicine. A strong suspicion of spirocercosis is usually evident after a thorough clinical examination and radiography of the chest has been performed. Lesions seen on radiography include an oesophageal mass, spondylitis and oesophageal air. Unfortunately, radiography is not diagnostic and additional diagnostic procedures are required to confirm the diagnosis. Endoscopy is commonly performed to diagnose the condition. The dog presented in this study had radiographic and clinical signs consistent with spirocercosis and definitive diagnosis was required. Shortly after sedation with medetomidine, the dog went into cardiac arrest and failed to respond to resuscitative measures. On post mortem, the diagnosis of spirocercosis was confirmed and the cause of death was identified as acute aortic rupture. Aortic aneurysms are not an uncommon finding and cause of acute death in dogs with spirocercosis. The acute rupture of the aorta in this case is most probably the result of cardiovascular changes associated with the administration of medetomidine. Medetomidine causes an acute rise in systemic vascular resistance with hypertension. The increase in shear stress across the weakened aortic wall resulted in rupture. Caution with the use of medetomidine in patients with spirocercosis is advised.     

Efficacy of daily oral ivermectin in the treatment of 10 cases of generalized demodicosis in adult dogs

Abstract The purpose of this study was to evaluate the efficacy of oral ivermectin at the dosage of 0.35 mg kg^-1 day^-1 for the treatment of generalized demodicosis in 10 adult dogs. Five of these 10 dogs had failed to respond to previous topical amitraz therapy. The mean time to obtain negative skin scrapings was 2.7 months and the mean duration of treatment was 4 months (range 2.5–8.5 months). Three patients (30%) were cured and they remained free of mites within 1 year follow-up. Two dogs (20%) were in remission for less than 6 months and five dogs (50%) relapsed. These five cases that relapsed were retreated with the above dosage of ivermectin and topical amitraz solution (1 mL Taktic/30 mL mineral oil) applied to site(s) of recurrence. One of these five cases that relapsed was in remission for more than 6 months, two dogs were in remission for less than 6 months and two dogs are still receiving treatment. Résumé— Le propos de cette étude est d'évaluer l'efficacieté de l'ivermectine par voie orale à un dosage de 0,35 mg/kg/jour dans le traitement de la démodécie généralisée chez 10 chiens adultes. Cinq de ces chiens n'avaient pas répondu à une thérapeutique topique préalable à l'amitraz. Le délai moyen pour obtenir la négativation des raclages cutanés est de 2,7 mois, et la durée moyenne de traitement est de 4 mois (extrême 2,5–8,5 mois). Trois patients (30%) ont été guéris et n'ont pas rechuté dans l'année qui a suivi le traitement. Deux des chiens (20%) ont été en rémission pendant moins de 6 mois et 5 chiens (50%) ont rechuté. Ces 5 chiens qui ont rechuté ont été retraités avec l'ivermectine à la même posologie associée à une thérapeutique topique à l'amitraz (1 ml de Taktic dans 30 ml d'huile minérale), appliquée aux sites de rechute. Un de ces 5 chiens fut en rémission pendant plus de 6 mois, 2 chiens pendant moins de 6 mois, enfin, les deux derniers reçoivent encore le traitement. [Fondati, A. Efficacy of daily oral ivermectin in the treatment of 10 cases of generalized demodicosis in adult dogs (Efficacité de l'ivermectine administrée oralement tous les jours dans le traitement de 10 cas de démodécie généralisée du chien adulte). Veterinary Dermatology 1996; 7 : 99–104.] Resumen El objetivo de este estudio fue evaluar la eficacia de la ivermectina oral con una dosis de 0.35 mg/Kg-dia para el tratamiento de la demodicosis generalizada en 10 perros adultos. Cinco de los 10 perros no habian respondido previamente a la terapia tópica con amitraz. El tiempo medio de obtención de raspados cutáneos negativos fue de 2.7 meses y la duratión media del tratamiento, de 4 meses (de 2.5 a 8.5 meses). Tres pacientes (30%) se curaron y permanecieron sin ácaros en un año de seguimiento. Dos perros (20%) estuvieron en remisión durante menos de 6 meses y en cinco (50%) se produjeron recaidas. Los animales que recayeron fueron tratados con la dosis de Ivermectina especificada arriba y solutión tópica de amitraz (1 mL Taktic/30 mL aceite mineral) aplicado a la(s) zona(s) de recidiva. Uno de los casos que recayó había estado en remisión durante 6 meses, dos perros estuvieron en remisión durante menos de 6 meses y dos estan aún bajo tratamiento. [Fondati, A. Efficacy of daily oral ivermectin in the treatment of 10 cases of generalized demodicosis in adult dogs (Eficacia de la Ivermectina oral en dosis diarias en el tratamiento de 10 casos de demodicosis generalizada en perros adultos). Veterinary Dermatology 1996; 7 : 99–104.] Zusammenfassung— Zweck dieser Studie war, die Wirksamkeit von oralem Ivermectin mit einer Dosierung von 0,35 mg/kg und Tag bei der Behandlung von generalisierter Demodikose bei 10 erwachsenen Hunden auszuwerten. 5 dieser 10 Hunden hatten auf eine vorausgegangene topische Amitraz-Therapie nicht angesprochen. Die Durchschnittszeit, um negative Hautgeschabsel zu erhalten, lag bei 2,7 Monaten, die Durchschnittsdauer der Behandlung bei 4 Monaten (mit einer Spannweite von 2,5 bis 8,5 Monaten). 3 Patienten (30%) wurden geheilt und blieben innerhalb des überwachungszeitraumes von 1 Jahr milbenfrei. Zwei Hunde (20%) waren in Remission für weniger als 6 Monate und 5 Hunde (50%) hatten ein Rezidiv. Diese fünf Rezidivfälle wurden mit der oben genannten Dosis Ivermectin und topischer Amitraz-Lösung (1 ml Taktic/30 ml Mineralöl) an den Stellen erneuter Veränderungen behandelt. Einer dieser fünf Rezidivfälle war in Remission für mehr als 6 Monate, zwei Hunde waren in Remission für weniger als 6 Monate und zwei Hunde sind immer noch unter Therapie. [Fondati, A. Efficacy of daily oral ivermectin in the treatment of 10 cases of generalized demodicosis in adult dogs (Wirksamkeit einer täglichen oralen Ivermectingabe bei der Behandlung von 10 Fällen von generalisierter Demodikose bei erwachsenen Hunden). Veterinary Dermatology 1996; 7 : 99–104.]     

Outcome following treatment of vertebral tumors in 20 dogs (1986-1995)

Twenty dogs with histopathologically confirmed primary (n=15) or metastatic (n=5) osteosarcoma (n=14) or fibrosarcoma (n=6) of the vertebral column were treated with surgery (n=4), radiation therapy and chemotherapy (n=6), surgery and chemotherapy (n=2), or surgery, radiation, and chemotherapy (n=8). All dogs died due to their disease; 15 died due to local failure, and five died due to nonvertebral metastasis. Overall median survival time was 135 days, with a range of 15 to 600 days. Of the factors evaluated, only postoperative neurological status had a significant influence on outcome by multivariate analysis. This study supports the overall guarded prognosis for dogs with vertebral neoplasia. Better combinations of surgery, chemotherapy, and radiation therapy remain to be defined for this difficult subset of animal cancer.     

Spirocerca lupi in dogs: prophylactic effect of doramectin

Spirocerca lupi is primarily a parasite of dogs, which typically causes oesophageal nodules, aortic aneurysms, and spondylitis. This study investigated the efficacy of doramectin as a prophylactic agent for canine spirocercosis. Five beagle dogs were injected subcutaneously with doramectin (400 μg/kg on 3 occasions 30 days apart q30d), while 5 other beagle dogs served as untreated controls. All dogs were inoculated with 40 infectious S. lupi larvae (L₃) one month after the last doramectin treatment. All control dogs and 4/5 treated dogs became infected. Two control dogs died of ruptured aortic aneurysms, while no deaths occurred in treated dogs. Oesophageal nodules appeared 40–103 day later in treated as compared to control dogs, and eggs appeared in the faeces 49–106 day later in treated as compared to control dogs. The mean faecal egg count on day 223 in the treatment group was reduced by 99.77%. All control dogs had thoracic radiographic changes during the study, while only 2/5 study dogs showed radiographic changes. This study shows that although doramectin did not entirely prevent canine spirocercosis it reduced the clinical signs associated with infection and delayed and reduced egg output.     

Compliance with short-term oral antibacterial drug treatment in dogs

Compliance with a 10-day course of oral antibacterial drugs in dogs being treated as outpatients at a veterinary clinic was assessed by use of pill count data obtained by telephone interview. The association between compliance and several possible determinants of compliance was investigated. Ninety-five animal owners were included in the study, with 44 per cent reporting 100 per cent compliance with the treatment regimen and as many as 88 per cent reporting a compliance level of 80 per cent or more. The compliance level was significantly higher (P < 0.002) when the animal owners felt that the veterinarians spent enough time on the consultation. Moreover, compliance was significantly higher (P < 0.05) for dogs being treated for gastrointestinal infections compared with those being treated for other diseases.     

Plasma pharmacokinetics and faecal excretion of ivermectin, doramectin and moxidectin following oral administration in horses

The present study was carried out to investigate whether the pharmacokinetics of avermectins or a milbemycin could explain their known or predicted efficacy in the horse. The avermectins, ivermectin (IVM) and doramectin (DRM), and the milbemycin, moxidectin (MXD), were each administered orally to horses at 200 microg/kg bwt. Blood and faecal samples were collected at predetermined times over 80 days (197 days for MXD) and 30 days, respectively, and plasma pharmacokinetics and faecal excretion determined. Maximum plasma concentrations (Cmax) (IVM: 21.4 ng/ml; DRM: 21.3 ng/ml; MXD: 30.1 ng/ml) were obtained at (tmax) 7.9 h (IVM), 8 h (DRM) and 7.9 h (MXD). The area under the concentration time curve (AUC) of MXD (92.8 ng x day/ml) was significantly larger than that of IVM (46.1 ng x day/ml) but not of DRM (53.3 ng x day/ml) and mean residence time of MXD (17.5 days) was significantly longer than that of either avermectin, while that of DRM (3 days) was significantly longer than that of IVM (2:3 days). The highest (dry weight) faecal concentrations (IVM: 19.5 microg/g; DRM: 20.5 microg/g; MXD: 16.6 microg/g) were detected at 24 h for all molecules and each compound was detected (> or = 0.05 microg/g) in faeces between 8 h and 8 days following administration. The avermectins and milbemycin with longer residence times may have extended prophylactic activity in horses and may be more effective against emerging and maturing cyathostomes during therapy. This will be dependent upon the relative potency of the drugs and should be confirmed in efficacy studies.     

Evaluation of once daily treatment with cyclosporine for anal furunculosis in dogs

Twenty-four dogs with anal furunculosis were treated with cyclosporine once daily for 13 weeks at dosages of 1.5, 3.0, 5.0 or 7.5 mg/kg, and re-examined after six and 12 months. After 13 weeks the disease in six of the dogs was in remission, 11 were controlled or improved and seven had failed to respond. The response of the dogs given the highest dose was significantly better than the response of the other groups taken together (P < 0.014), and better than the responses of the groups given 1.5 mg/kg and 5 mg/kg (P < 0.05). The dogs improved clinically during the treatment, most rapidly during the first five weeks. Of the six dogs that were in remission after 13 weeks, three relapsed after one, two and six months. The 11 dogs that were improved or controlled after 13 weeks were either left untreated or were continued on cyclosporine medication for one to three months at a dosage of 1.5 to 7.5 mg/kg; the disease went into remission in four cases and remained controlled in the other seven, but four of the 11 cases relapsed during the 12 months following the treatment. The side effects observed included increased coat turnover and transient vomiting.     

Sheep scab--environmental considerations of treatment with doramectin.

The paper reviews the recent change in attitudes to dipping sheep and the proposed legal requirements to prevent and treat sheep scab. The implications of fulfillment of all the requirements of the European Groundwater Directive and the probable resultant increase of the use of injectable endectocides as an alternative to plunge dipping are discussed in relation to their likely frequency of use and potential ecological impact. In particular the properties of doramectin, one of the most recently introduced, are examined in relation to its use for the treatment of sheep scab.     

The pharmacokinetics of clomipramine and desmethylclomipramine in dogs: parameter estimates following a single oral dose and 28 consecutive daily oral doses of clomipramine

Clomipramine is a tricyclic antidepressant that has been recommended for the treatment of canine compulsive disorder. The pharmacokinetics of clomipramine in dogs have not been reported. This study describes the pharmacokinetics of clomipramine and its active metabolite, desmethylclomipramine, in six male dogs. Serial blood samples were collected following both a single oral dose of clomipramine (3 mg/kg) and 28 consecutive daily oral doses (3 mg/kg q 24 h). In addition, 'peak' and 'trough' samples were taken throughout the 28-day dosing period. Plasma was assayed for total (free and protein-bound) clomipramine and desmethylclomipramine, using gas-chromatography with mass spectrometric detection. Various pharmacokinetic parameters were then determined. Following a single dose of clomipramine, time of maximum plasma concentration ( t _max) of clomipramine was 0.75–3.1 h, maximum plasma concentration ( C _max) was 16–310 ng/mL and elimination half-life ( t _1/2el) was 1.2–16 h; t _max of desmethylclomipramine was 1.4–8.8 h, C _max was 21–134 ng/mL and t _1/2el was 1.2–2.3 h. Following multiple dosing, there was a numeric increase in these parameters; t _max of clomipramine was 3–8 h, C _max was 43–222 ng/mL and t _1/2el was 1.2–16 h; t _max of desmethylclomipramine was 1.4–8.8 h, C _max was 21–134 ng/mL and t _1/2el was 1.2–2.3 h. Clinically significant differences between dogs and humans in the pharmacokinetics of oral clomipramine are discussed.