Efficacy of injectable maropitant (Cerenia™) in a randomized clinical trial for prevention and treatment of cisplatin-induced emesis in dogs presented as veterinary patients

Chemotherapy‐induced nausea and vomiting (CINV) is a common side‐effect of cisplatin therapy. Maropitant (Cerenia?), a novel neurokinin‐1 receptor antagonist, was evaluated for prevention and treatment of cisplatin‐induced emesis in tumour‐bearing dogs. Dogs (n= 122) were randomly allocated to three treatment groups: T01, placebo before and after cisplatin; T02, placebo before and maropitant after cisplatin; or T03, maropitant before and placebo after cisplatin. Maropitant treatment (T02) following a cisplatin‐induced‐emetic event resulted in significantly fewer subsequent emetic events (P= 0.0005) than in placebo‐treated dogs (T01). In placebo‐treated (T01) dogs, 56.4% were withdrawn from the study because of treatment failure compared with 5.3% in group T02. When maropitant was administered prior to cisplatin treatment (T03) in a prevention regime, 94.9% did not vomit compared with only 4.9% of placebo‐treated dogs, and significantly fewer emetic events (P < 0.0001) were observed in those dogs that did vomit. In summary, maropitant was safe and highly effective in reducing or completely preventing cisplatin‐induced emesis.     

Efficacy of maropitant in the prevention of delayed vomiting associated with administration of doxorubicin to dogs

Background: Vomiting, nausea, inappetence, and diarrhea are common delayed adverse effects of doxorubicin. Maropitant, a neurokinin‐1 receptor antagonist, is known to prevent acute vomiting in dogs receiving cisplatin. Objective: To evaluate the efficacy of maropitant in preventing delayed vomiting after administration of doxorubicin to dogs. Animals: Fifty‐nine dogs with cancer. Methods: This randomized, double‐blind, placebo‐controlled study used a cross‐over design. Dogs were randomized into 1 of 2 treatment groups. Group A received maropitant after the 1st doxorubicin, and placebo after the 2nd. Group B received placebo first, and maropitant second. Maropitant (2 mg/kg) or placebo tablets were administered PO for 5 days after doxorubicin treatment. Owners completed visual analog scales based on Veterinary Cooperative Oncology Group‐Common Terminology Criteria for Adverse Events to grade their pet's clinical signs during the week after administration of doxorubicin. Statistical differences in gastrointestinal toxicosis and myelosuppression between maropitant and placebo treatments were evaluated. Results: Significantly fewer dogs had vomiting (P= .001) or diarrhea (P= .041), and the severity of vomiting (P < .001) and diarrhea (P= .024) was less the week after doxorubicin when receiving maropitant compared with placebo. No differences were found between maropitant and placebo for other gastrointestinal and bone marrow toxicoses. Conclusions and Clinical Importance: Maropitant is effective in preventing delayed vomiting induced by doxorubicin. Its prophylactic use might improve quality of life and decrease the need for dose reductions in certain dogs.     

Efficacy of maropitant for preventing vomiting associated with motion sickness in dogs

Maropitant is a neurokinin-1 inhibitor that acts to prevent and treat vomiting by blocking stimuli to the final common pathway in the emetic centre of the brain. The field efficacy and safety of a single oral dose of maropitant were investigated for the prevention of vomiting in dogs with a history of motion sickness resulting from transportation by car in two blinded, placebo-controlled studies. In an exploratory study designed as a two-way crossover trial with 17 dogs, 10 of the dogs given the placebo vomited during a car journey but only three of the dogs vomited under maropitant treatment. In a larger multicentred parallel design study, 69 of 105 dogs treated with the placebo vomited during the journey compared with 15 of 106 dogs treated with maropitant (P < 0.0001).     

Comparative efficacy of maropitant and selected drugs in preventing emesis induced by centrally or peripherally acting emetogens in dogs

Maropitant (Cerenia^?; a novel, selective neurokinin₁ receptor antagonist), chlorpromazine, metoclopramide and ondansetron were compared in two randomized, placebo‐controlled studies for efficacy in preventing emesis induced by emetogens acting centrally (apomorphine; Study 1) or peripherally (syrup of ipecac; Study 2) in dogs. In each study, ten male and ten female beagles were treated in a five‐treatment, five‐period crossover design. The five treatments were 0.9% saline (0.1 mL/kg), maropitant (1 mg/kg), metoclopramide (0.5 mg/kg), or chlorpromazine (0.5 mg/kg) all administered subcutaneously, or ondansetron (0.5 mg/kg) administered intravenously. One hour posttreatment dogs were challenged with apomorphine at 0.1 mg/kg intravenously (Study 1) or syrup of ipecac at 0.5 mL/kg orally (Study 2). Following emetogen challenge, dogs were observed for 30 min (Study 1) or 1 h (Study 2) for emesis. No clinical signs, other than those related to emesis, were observed. Efficacy of maropitant in preventing emesis induced centrally by apomorphine was not different (P > 0.05) from metoclopramide or chlorpromazine but was superior (P < 0.0001) to ondansetron. Efficacy of maropitant in preventing emesis induced by syrup of ipecac was not different (P > 0.05) from ondansetron but was superior (P ≤ 0.0102) to metoclopramide or chlorpromazine. Maropitant was effective (P < 0.0001 relative to control) in preventing vomiting caused by stimulation of either central or peripheral emetic pathways, whereas the other drugs examined prevented vomiting caused by central (metoclopramide and chlorpromazine; P < 0.0001) or peripheral (ondansetron; P < 0.0001) stimulation but not both.     

Efficacy of maropitant in preventing vomiting in dogs premedicated with hydromorphone

ObjectiveThe goal of this study was to evaluate the effectiveness of maropitant (Cerenia^®) in preventing vomiting after premedication with hydromorphone.Study designRandomized, blinded, prospective clinical study.AnimalsEighteen dogs ASA I/II admitted for elective orthopedic surgical procedures. The dogs were a mixed population of males and females, purebreds and mixed breeds, 1.0–10.2 years of age, weighing 3–49.5 kg.MethodsDogs were admitted to the study if they were greater than 1 year of age, healthy and scheduled to undergo elective orthopedic surgery. Dogs were randomly selected to receive one of two treatments administered by subcutaneous injection. Group M received 1.0 mg kg^?1 of maropitant, Group S received 0.1 mL kg^?1 of saline 1 hour prior to anesthesia premedication. Dogs were premedicated with 0.1 mg kg^?1 of hydromorphone intramuscularly. A blinded observer documented the presence of vomiting, retching and/or signs of nausea for 30 minutes after premedication.ResultsAll dogs in S vomited (6/9), retched (1/9) or displayed signs of nausea (2/9). None (0/9) of the dogs in M vomited, retched or displayed signs of nausea. Dogs in M had significantly fewer incidences of vomiting (p = 0.0090), vomiting and retching (p = 0.0023) and vomiting, retching and nausea (p < 0.0001) when compared to S.Conclusion and clinical relevanceMaropitant prevents vomiting, retching and nausea associated with intramuscular hydromorphone administration in dogs.     

Comparative efficacy of metoclopramide,ondansetron and maropitant in preventing parvoviral enteritis‐induced emesis in dogs

The aim of the study was to evaluate the efficiencies of selected anti‐emetic drugs (metoclopramide, ondansetron and maropitant) in preventing vomiting in the treatment of canine parvoviral enteritis. We designed a randomized, prospective clinical study. PVE quick ELISA test‐positive dogs between 4 and 12 months of age were included in the study. Each of metoclopramide, ondansetron, maropitant and control group had 8 dogs. Metoclopramide and ondansetron were administered as 0.5 mg/kg doses three times a day via intravenous route, and maropitant was administered as 1 mg/kg doses once a day subcutaneously. The number and severity of daily vomitings were recorded. All dogs were treated and monitored for five days; treatments were continued until all animals healed. Metoclopramide, ondansetron and maropitant decreased the severity of vomiting from the first day and the vomiting numbers from the third day in PVE treatment. Obtained results showed that maropitant can be used successfully such as metoclopramide and ondansetron, which are frequently used for PVE treatment. At the same time, it was discovered that metoclopramide, ondansetron and maropitant were equally effective in reducing the frequency and severity of vomiting.     

The anti-emetic efficacy of maropitant (Cerenia) in the treatment of ongoing emesis caused by a wide range of underlying clinical aetiologies in canine patients in Europe

OBJECTIVES: The efficacy of maropitant (Cerenia; Pfizer Inc.) as an anti-emetic for use in dogs with ongoing emesis was evaluated in a two-phase multi-centric study conducted at veterinary clinics in France, Italy, Slovakia and the UK. METHODS: In phase I, dogs with ongoing emesis were randomised in a 1:1 ratio to either maropitant (32 dogs) or metoclopramide (34 dogs). In phase II, dogs were randomised in a 2:1 ratio to maropitant (77 dogs) or metoclopramide (40 dogs). Maropitant was administered subcutaneously at 1 mg/kg/day for up to five days. Metoclopramide was administered as recommended on the product labels as licensed at 0.5 to 1 mg/kg/day subcutaneously or orally with the daily dose divided over two to three administrations per day for up to three to five days. RESULTS: In phase I, 97 per cent of dogs treated with maropitant and 71 per cent of dogs treated with metoclopramide did not vomit after treatment (P<0.01). The mean number of emetic events after maropitant treatment was significantly reduced compared with that after metoclopramide treatment (P=0.01). In phase II, the occurrence of emesis was lower for maropitant during the first 24 hours (P<0.0001) and for each day thereafter. CLINICAL SIGNIFICANCE: A single daily dose of maropitant was more effective than metoclopramide administered two or three times daily in the treatment of emesis caused by various aetiologies in dogs.     

Efficacy and safety of maropitant,a selective neurokinin1 receptor antagonist,in two randomized clinical trials for prevention of vomiting due to motion sickness in dogs

Maropitant (Cerenia^TM), a selective neurokinin₁ receptor antagonist, was evaluated for efficacy and safety in prevention of vomiting due to motion sickness in dogs in two randomized clinical trials. One‐hundred eighty‐nine dogs with a history of motion sickness were enrolled at 26 veterinary clinics (across 12 US states) across the two trials; of these, 163 were fully evaluable, 19 were evaluable only for safety, and seven were not evaluable. Each trial used a two‐period crossover design. Each dog was treated orally with placebo or maropitant (minimum dose of 8 mg/kg body weight using unit dosing) tablets at approximately 2 h (Trial 1) or 10 h (Trial 2) before an automobile ride of approximately 60 min, during which dogs were observed for signs of motion sickness. Following a 10–14‐day washout period, each dog was administered the opposite treatment and taken for another journey (same route, driver and vehicle). Maropitant reduced the occurrence of vomiting compared to placebo by 86.1% or 76.5% when given approximately 2 or 10 h prior to travel, respectively. No significant clinical signs were observed after maropitant treatment. Maropitant was safe and effective in preventing vomiting due to motion sickness in dogs when administered at a minimum dose of 8 mg/kg body weight as oral tablets 2 or 10 h prior to travel.     

Safety, pharmacokinetics and use of the novel NK-1 receptor antagonist maropitant (Cerenia) for the prevention of emesis and motion sickness in cats

The present study characterizes the safety, pharmacokinetics, and anti-emetic effects of the selective NK-1 receptor antagonist maropitant in the cat. Safety of maropitant was determined following 15 days of subcutaneous (SC) administration at 0.5–5 mg/kg. Maropitant was well tolerated in cats at doses that exceeded the efficacious anti-emetic dose range of the drug by at least a factor of 10 and adverse clinical signs or pathological safety findings were not noted at any dose.The pharmacokinetics of maropitant in cats were determined following single dose oral (PO), intravenous (IV) and SC administration. Maropitant had a terminal half-life of 13–17 h and a bioavailability of 50 and 117% when administered PO and SC, respectively. Efficacy was determined against emesis induced either by xylazine or by motion. A dosage of 1 mg/kg maropitant administered IV, SC or PO prevented emesis elicited by xylazine. The compound had good oral antiemetic activity and a long (24 h) duration of action. Maropitant (1.0 mg/kg) was highly effective in preventing motion-induced emesis in cats. These studies indicate that the NK-1 receptor antagonist maropitant is well tolerated, safe and has excellent anti-emetic properties in cats.     

Use of cisplatin for treatment of appendicular osteosarcoma in dogs

Nineteen dogs were treated for osteosarcoma of the appendicular skeleton. Eleven dogs treated by amputation and adjunctive cisplatin chemotherapy had a significantly longer (P less than 0.003) median survival time of 43 weeks (range, 20 to 108 weeks) than did 8 dogs whose median survival time was 14.5 weeks (range, 8 to 46 weeks) after amputation alone. All 11 dogs given cisplatin were evaluated for signs of drug toxicosis. Transient episodes of vomiting were recorded in 9 of 11 dogs. Additional toxic effects included gradual decreases in endogenous creatinine clearance in 3 dogs and thrombocytopenia in 1 dog. On the basis of prolonged survival times and minimal adverse effects, we concluded that cisplatin has promise as an effective and relatively nontoxic agent, when combined with amputation, for treatment of dogs with osteosarcoma of the appendicular skeleton.     

Pharmacokinetics of gemcitabine and its primary metabolite in dogs after intravenous infusion

Gemcitabine is a relatively new chemotherapeutic compound used to treat a variety of cancers in dogs. Previous work presented in a companion paper explored the plasma kinetics of gemcitabine and its inactive metabolite, 2',2'-difluorodeoxyuridine (dFdU), in dogs after an intravenous bolus gemcitabine dose and demonstrated the saturation of intracellular dFdCTP (2',2'-difluorodeoxycytidine 5'-triphosphate) occurs in vitro with increasing extracellular gemcitabine exposure in canine melanoma cells. In this study, the plasma pharmacokinetics (PKs) of gemcitabine and dFdU are further explored after gemcitabine doses of 10, 30, and 60 mg/kg administered by intravenous infusion with a loading dose. Gemcitabine displayed linear PKs, while the kinetics of dFdU were not dose proportional. The overall clearance, volume of distribution at steady-state, and terminal elimination half-life (t(1/2)) for gemcitabine were 0.421 L/h.kg, 0.822 L/kg, and 1.49 h, respectively. Plasma concentrations of dFdU peaked at approximately 2 h postdosing and had a t(1/2) of 14.9 h.     

Bispectral index in dogs at three intravenous infusion rates of propofol

ObjectiveTo establish the correlation between the bispectral index (BIS) and different rates of infusion of propofol in dogs.Study designProspective experimental trial.AnimalsEight adult dogs weighing 6–20 kg.MethodsEight animals underwent three treatments at intervals of 20 days. Propofol was used for induction of anesthesia (10 mg kg⁻¹ IV), followed by a continuous rate infusion (CRI) at 0.2 mg kg⁻¹ minute⁻¹ (P2), 0.4 mg kg⁻¹ minute⁻¹ (P4) or 0.8 mg kg⁻¹ minute⁻¹ (P8) for 55 minutes. The BIS values were measured at 10, 20, 30, 40, and 50 minutes (T10, T20, T30, T40, and T50, respectively) after the CRI of propofol was started. Numeric data were submitted to analysis of variance followed by Tukey test (p < 0.05).ResultsThe BIS differed significantly among groups at T40, when P8 was lower than P2 and P4. At T50, P8 was lower than P2. The electromyographic activity (EMG) in P2 and P4 was higher than P8 at T40 and T50.ConclusionsAn increase in propofol infusion rates decreases the BIS values and EMG.     

Pharmacokinetics of fentanyl after single intravenous injection and constant rate infusion in dogs

OBJECTIVE: To determine the plasma concentration and define the pharmacokinetic characteristics of fentanyl (10 microg kg(-1)) administered as a single intravenous (IV) injection followed by: (a) no further drug; or (b) a constant rate infusion (CRI) of fentanyl 10 microg kg(-1) hour(-1) lasting 1, 3 or 4 hours in dogs. Animals Fourteen healthy adult beagles (seven males and seven females). EXPERIMENTAL DESIGN: Randomized cross-over design. MATERIALS AND METHODS: Dogs were randomly assigned to four treatment groups. Drugs were administered to each dog in a randomized cross-over design with at least a 14-day washout interval between experiments. All dogs received an IV loading dose of fentanyl (10 microg kg(-1)). One group received no further fentanyl. In others, the loading dose was followed by a CRI of fentanyl (10 microg kg(-1) hour(-1)) for 1, 3 or 4 hours. Blood samples were collected and plasma fentanyl concentrations determined using high-performance liquid chromatography-mass spectrometry. Plasma pharmacokinetic estimates were obtained by plotting plasma concentrations versus time data and by fitting the change in concentration to a pharmacokinetic model, using a purpose-built program written by the Graduate School of Pharmaceutical Sciences (Kyoto University) in Visual Basic (VBA) on Excel (Microsoft Corporation). RESULTS: Plasma fentanyl concentration decreased rapidly after single IV injection: the plasma concentration-time curve best fitted a two-compartment model. Pharmacokinetic variables for IV injection were characterized by a short distribution half-time (t1/2alpha was 4.5 minutes), a relatively long elimination half time (t1/2beta was 45.7 minutes), a large volume of distribution (approximately 5 L kg(-1)) and high total body clearance (77.9 mL minute(-1) kg(-1)). Stable plasma fentanyl levels were obtained in all CRI groups although pharmacokinetic variables were influenced by the duration of administration. CONCLUSIONS AND CLINICAL RELEVANCE: While this study clarified the pharmacokinetic features of rapid IV fentanyl injection and CRI in dogs, the plasma concentration achieving analgesia was not and so further research is needed. Further studies on the effects of other sedatives and/or anaesthetics on fentanyl's disposition are also required as the drug is commonly used with other agents.     

Intranasal infusion of enilconazole for treatment of sinonasal aspergillosis in dogs

OBJECTIVE: To determine effectiveness of infusion of 1 and 2% enilconazole for treatment of nasal and sinusal aspergillosis, respectively, in dogs. DESIGN: Case series. ANIMALS: 26 client-owned dogs with aspergillosis. PROCEDURE: All dogs had typical clinical signs of aspergillosis and rhinoscopically visible intrasinusal or intranasal fungal plaques associated with turbinate destruction. During rhinoscopy, affected nasal cavities and frontal sinuses were debrided meticulously. Nineteen dogs (group A) were treated with 1% enilconazole by use of a modified noninvasive infusion procedure. Seven dogs (group B) were treated with 2% enilconazole via catheters that were placed via endoscopic guidance into the frontal sinuses. All dogs underwent follow-up rhinoscopy for determination of further treatment until cure was established. RESULTS: Age, disease duration, clinical score, and rhinoscopic score were similar for both groups before treatment. In group A, 17 of 19 dogs were cured; 9, 6, and 2 dogs were cured after 1, 2, or 3 treatments, respectively. The remaining 2 dogs were euthanatized before the end of the treatment protocol. In group B, all dogs were cured; 6 dogs and 1 dog were cured after 1 or 2 treatments, respectively. Only minor adverse effects such as nasal discharge, epistaxis, and sneezing developed. CONCLUSIONS AND CLINICAL RELEVANCE: After extensive rhinoscopic debridement, 1 and 2% enilconazole infused into the nasal cavities and the frontal sinuses, respectively, were effective for treatment of aspergillosis in dogs. Intrasinusal administration via endoscopically placed catheters appeared to require fewer infusions for success. Follow-up rhinoscopy is strongly advised.     

Palliative intravenous cisplatin treatment for concurrent peritoneal and pleural mesothelioma in a dog

A 10-year-old Maltese dog was presented with abdominal distention and dyspnea. Cytological examination of pleural and peritoneal effusion was suggestive of malignant effusion of glandular origin. Numerous, multifocal, tan to white nodules were disseminated throughout the surface of the abdominal organs and peritoneum at biopsy. Histologically, the tumors were revealed to be an epithelial type of mesothelioma. Neoplastic cells co-expressed cytokeratin and vimentin. Intravenous administration of cisplatin was chosen as the treatment. During treatment, the dog's overall body condition improved and the clinical signs were relieved without significant side effects. The survival time from diagnosis to sudden death by unknown cause was 153 days.     

Pharmacokinetics and physiological effects of two intravenous infusion rates of morphine in conscious dogs

This study examined the pharmacokinetics and physiologic effects of two infusions rates of morphine in conscious dogs. Five adult dogs were randomly studied at weekly intervals. An initial dose of either 0.3 or 0.6 mg/kg were each followed by infusions of 0.17 and 0.34 mg/kg/h. Plasma morphine concentrations, physiological parameters, sedation and mechanical antinociception were evaluated during each infusion. Morphine was assayed by high pressure liquid chromatography (HPLC) with electrochemical coulometric detection and pharmacokinetic parameters were calculated. Data were fitted to a bi-compartment model with a rapid distribution (<1 min for both doses) and slower termination rate. For the high and low doses, respectively, mean+/-SD terminal half-life was 38+/-5 and 27+/-14 min, apparent volumes of distribution at steady-state were 1.9+/-0.5 and 1.3+/-0.8 L/kg, with clearances of 50+/-15 and 67+/-20 mL/kg/min. Steady-state plasma concentrations ranged from 93 to 180 ng/mL and 45 to 80 ng/mL in the high and low doses, respectively. Respiratory rate increased significantly, pulse oximetry remained>95% and body temperature decreased significantly during both infusions. No vomition or neuroexcitation occurred. Sedation and mechanical antinociception were both mild during the lower infusion rate, and mild to moderate during the higher infusion rate. In conclusion, morphine pharmacokinetics was not altered by increasing infusion rates, producing stable, long-lasting plasma concentrations.     

Surgical treatment of lumbosacral instability caused by discospondylitis in four dogs

OBJECTIVE: To describe a surgical technique involving distraction and stabilization of the lumbo-sacral vertebral segment using an external skeletal fixator in dogs with lumbosacral instability caused by discospondylitis. STUDY DESIGN: Retrospective clinical study. ANIMALS: Four client-owned dogs. METHODS: Medical records of all dogs diagnosed with discospondylitis from 1994 to 1997 were identified and reviewed. Four dogs with lumbosacral discospondylitis requiring surgical treatment were then specifically studied. Surgical technique, clinical signs, preoperative diagnostic investigation, radiographic findings, and the results of short-term and long-term reevaluations were recorded. RESULTS: Twelve dogs with discospondylitis were identified, 4 of which had lumbosacral discospondylitis. These 4 dogs underwent surgical distraction and stabilization because they failed to respond to medical treatment. Three dogs received a cancellous bone graft between L7 and S1 and had rapid interbody fusion of this vertebral segment. The dog that did not receive a graft did not have interbody fusion at the time of fixator removal. This did not affect the final clinical outcome. Lumbosacral pain and neurological deficits present before surgery rapidly subsided after the procedure. All dogs received concurrent antibiotic treatment for a minimum of 4 weeks. All dogs were clinically normal at the time of fixator removal and all continued to do well during the follow-up period (8-48 months; mean, 27.5 months). CONCLUSION AND CLINICAL RELEVANCE: Lumbosacral discospondylitis may not respond well to conservative treatment because of the mobility of the affected space. Surgical treatment involving distraction and stabilization to obtain intervertebral fusion is very effective in treating lumbosacral instability caused by discospondylitis.     

Safety and efficacy of an ocular insert for apomorphine-induced emesis in dogs

OBJECTIVE: To evaluate the safety and efficacy of an ocular insert designed to provide controlled release of apomorphine for the induction of emesis in dogs. ANIMALS: 5,001 dogs treated with ocular apomorphine inserts and 32 dogs treated with IV administration of apomorphine. PROCEDURES: Data collected on a case report form included breed, body weight, time to emesis after placement of the insert, and any information available regarding the nature of the toxicosis and clinical signs. A list of potential adverse effects was provided, and attending clinicians graded their occurrence by use of a subjective scale. Similar report forms were used for dogs that received apomorphine IV. Treatment was considered successful if emesis occurred within 15 minutes of administration. Safety was assessed by evaluation of the frequency and severity of adverse effects. RESULTS: For the ocular insert and IV injection groups, the success rates were 83.5% and 90.6% respectively, and were not significantly different. Adverse effects were more frequent in the IV group, whereas ocular irritation was most frequent in the insert group. CONCLUSIONS AND CLINICAL RELEVANCE: Overall, the ocular inserts provided an alternative to parenteral administration of apomorphine with comparable efficacy and a lower prevalence of adverse effects.