Anesthetic management of a dog undergoing unilateral adrenalectomy for phaeochromocytoma excision using a partial intravenous anesthetic protocol.

Background: The anesthetic management of adrenalectomies for phaeochromocytoma excision, a catecholamine-secreting tumor, is challenging due to the potential for fatal complications following severe hemodynamic variations, including hypertensive crisis following tumor manipulation or sympathetic stimulation, but also severe hypotension and volume depletion post resection. Case Description: An 11 kg, 15-year-old male neutered Jack Russel Terrier, with mitral valve disease stage B2, was referred for adrenalectomy for phaeochromocytoma resection. The patient was administered per os prazosin 0.11 mg/kg twice a day and amlodipine 0.125 mg/kg once a day for preoperative stabilization. On the day of surgery, the dog received maropitant 1 mg/kg intravenously (IV) and was premedicated with 0.2 mg/kg methadone IV. Anesthesia was induced with alfaxalone 1 mg/kg IV and midazolam 0.2 mg/kg IV and maintained with partial intravenous anesthesia using sevoflurane in 70% oxygen and constant rate infusions of dexmedetomidine 0.5 µg/kg/hour and maropitant 100 µg/kg/hour. After induction of anesthesia, the dog was mechanically ventilated, and a transversus abdominal plane block was performed with ropivacaine 0.2%. The dog remained remarkably stable with a single, self-limiting, hypertension episode recorded intraoperatively. Postoperative rescue analgesia consisted of methadone and ketamine. The dog was discharged 48 hours after surgery, but persistent hypertension was reported at suture removal. Conclusion: The use of a low-dose dexmedetomidine CRI, a maropitant CRI, and a transversus abdominal plane block provided stable perioperative hemodynamic conditions for phaeochromocytoma excision in a dog.

Does maropitant provide more effective perioperative pain management than meloxicam in bitches undergoing ovariohysterectomy? The first report on the comparison of visceral algesia-analgesia for ovariohysterectomy.

Ovariohysterectomy (OVH) is a widely used surgical procedure in small animal practice. In developing countries, injectable anesthetics such as ketamine and xylazine are commonly used in veterinary medicine. Pharmacological agents with analgesic activity, such as ketamine and meloxicam, are not sufficiently effective in reducing visceral pain. Therefore, this study aimed to investigate the visceral analgesia and anti-inflammatory effectiveness of maropitant compared with those of meloxicam during and after OVH in bitches. In this study, thirty-six bitches were randomly divided into the maropitant, meloxicam, and control groups. The heart rate (HR), peripheral oxygen saturation, and respiratory rate were monitored during the procedure. Pain scores were assessed using the University of Melbourne pain scale (UMPS). Rescue analgesia was not necessary for any bitch at any time point. Blood samples were collected before anesthesia induction and 24 h after the operation to determine C-reactive protein (CRP) levels. No significant difference was observed in HR between the control and meloxicam groups when the right ovary was removed, and the HR of the maropitant group was significantly (p < 0.05) lower than that of the control group. The pain scores of the maropitant group were significantly (p < 0.05) lower than those of the other groups. However, no significant differences were observed in CRP levels between the groups. In conclusion, compared to meloxicam, maropitant provided more effective visceral analgesia in bitches undergoing OVH, although no significant difference was found in its anti-inflammatory effect.

Cardiorespiratory Effects and Desflurane Requirement in Dogs Undergoing Ovariectomy after Administration Maropitant or Methadone.

General anesthesia for ovariectomy in dogs is based on a balanced anesthesia protocol such as using analgesics along with an inhalant agent. While opioids such as fentanyl and methadone are commonly used for their analgesic potency, other drugs can also have analgesic effects. Maropitant, an antiemetic for dogs and cats, has also been shown to exert analgesic effects, especially on visceral pain. The aim of this study was to compare the cardiorespiratory effects and analgesic properties of maropitant and methadone combined with desflurane in dogs undergoing ovariectomy. Two groups of 20 healthy mixed-breeds bitches undergoing elective ovariectomy received intravenous either maropitant at antiemetic dose of 1 mg kg-1 or methadone at the dose of 0.3 mg kg-1. Cardiorespiratory variables were collected before premedication, 10 min after sedation and during surgery. Recovery quality and postoperative pain were evaluated 15, 30, 60, 120, 240 and 360 min postoperatively. Results showed that maropitant produced analgesia and reduced the requirement of desflurane in amounts similar to those determined by methadone (5.39 ± 0.20% and 4.91 ± 0.26%, respectively) without significant difference, while maintaining heart rate, arterial blood pressure, respiratory rate and carbon dioxide end-tidal partial pressure even at a more satisfactory level. Therefore, maropitant may be recommended as an analgesic drug for abdominal surgery not only in healthy dogs but also in those with reduced cardiorespiratory compensatory capacities or at risk of hypotension, especially when combined with a sedative such as dexmedetomidine.

Pharmacokinetics of intramuscular maropitant in pigs (Sus scrofa domesticus).

Pigs are at risk of vomiting from medical conditions as well as the emetic side effects of drugs administered for peri-operative manipulations, but there is a lack of pharmacokinetic data for potential anti-emetic therapies, such as maropitant, in this species. The main objective of this study was to estimate plasma pharmacokinetic parameters for maropitant in pigs after a single intramuscular (IM) administration dosed at 1.0 mg/kg. A secondary objective was to estimate pilot pharmacokinetic parameters in pigs after oral (PO) administration at 2.0 mg/kg. Maropitant was administered to six commercial pigs at a dose of 1.0 mg/kg IM. Plasma samples were collected over 72 h. After a 7-day washout period, two pigs were administered maropitant at a dose of 2.0 mg/kg PO. Maropitant concentrations were measured via liquid chromatography/mass spectrometry (LC-MS/MS). A non-compartmental analysis was used to derive pharmacokinetics parameters. No adverse events were noted in any of the study pigs after administration. Following single IM administration, maximum plasma concentration was estimated at 412.7 ± 132.0 ng/mL and time to maximum concentration ranged from 0.083 to 1.0 h. Elimination half-life was estimated at 6.7 ± 1.28 h, and mean residence time was 6.1 ± 1.2 h. Volume of distribution after IM administration was 15.9 L/kg. Area under the curve was 1336 ± 132.0 h*ng/mL. The relative bioavailability of PO administration was noted to be 15.5% and 27.2% in the two pilot pigs. The maximum systemic concentration observed in the study pigs after IM administration was higher than what was observed after subcutaneous administration in dogs, cats, or rabbits. The achieved maximum concentration exceeded the concentrations for anti-emetic purposes in dogs and cats; however, a specific anti-emetic concentration is currently not known for pigs. Further research is needed into the pharmacodynamics of maropitant in pigs to determine specific therapeutic strategies for this drug.

Determination of the embryotoxic effect of maropitant using an in ovo model.

The aim of this research was to determine the embryotoxic and teratogenic effects and lethal dose (LD50) of maropitant in ovo, using fertile chicken eggs. The study was designed in two stages, CHEST-I and CHEST-II. For CHEST-I, 210 fertile eggs were divided into seven equal groups; control, saline solution and 5 different doses of maropitant (10, 5, 2.5, 1.25, 0.625 mg/kg) injected groups. For CHEST-II, 150 fertile eggs were divided into five equal groups; control, saline solution and 3 different doses of maropitant (8, 6, 4 mg/kg)-injected groups. Eggs were opened on day 21 of incubation. Maropitant did not cause teratogenicity at any dose, while higher embryonic death rates were observed at doses above 4 mg/kg. The LD50 dose of maropitant was determined as 7.24 mg/kg. In conclusion, maropitant should only be used after full consideration of risks and benefits in pregnancy.

Pharmacokinetics of maropitant citrate in Rhode Island Red chickens (Gallus gallus domesticus) following subcutaneous administration.

Maropitant citrate is a synthetic neurokinin-1 receptor antagonist and substance P inhibitor used for control of emesis in dogs in cats. Maropitant citrate is used empirically in birds, despite a lack of pharmacokinetic data in avian species. The objective of this study was to determine the pharmacokinetic profile of a single dose of maropitant citrate 1 and 2 mg/kg subcutaneously (SC) in eight Rhode Island Red hens (Gallus gallus domesticus). A crossover study design was used with 1-week washout between trials. Blood samples were collected over 36 h after drug administration. Plasma concentrations were measured using liquid chromatography-tandem mass spectrometry and pharmacokinetic parameters were determined via non-compartmental analysis. The mean maximum plasma concentration, time to maximum concentration, and elimination half-life following 1 and 2 mg/kg SC were 915.6 ± 312.8 ng/ml and 1195.2 ± 320.2 ng/ml, 0.49 ± 0.21 h and 1.6 ± 2.6 h, and 8.47 ± 2.24 h and 8.58 ± 2.6 h, respectively. Pharmacokinetic data suggests doses of 1 or 2 mg/kg SC may be administered every 12-24 h to maintain above target plasma concentration similar to dogs (90 ng/ml). These data provide a basis for further investigation of maropitant citrate pharmacokinetics and pharmacodynamics in birds.

Evaluation of the efficacy of transdermal administration of maropitant in managing vomiting in cats.

Background: Antiemetic maropitant is a widely used medication for treating acute and chronic vomiting in cats. It is available as tablets or injectable solution (Cerenia®). With the oral and injectable routes being especially difficult to pursue in cats experiencing vomiting and nausea, the transdermal administration might be an efficient alternative. The aim of this study was to demonstrate the antiemetic effect of maropitant administered via the transdermal route in cats. Case Description: There were 8 cats enrolled in this study, weighing between 2 and 7 kg, more than 6 months old, and experiencing at least 2 episodes of vomiting in the last 72 hours. Compounded transdermal maropitant was prepared using finely ground Cerenia® tablets, dissolved in propylene glycol and incorporated in the commercial liposomal base Pentravan® (Fagron®, Thiais, France). The uniformity of content was determined using the high performance liquid chromatography (HPLC) method. The product was administered at a dosage of 4 mg/cat once a day (QD), applied on the inner pinna of the ear for five consecutive days. Monitoring and evaluation of vomiting frequency and nausea were performed. A significant decrease in vomiting frequency was observed in 6 of the 8 enrolled cats. A reduction in nausea, associated with an improvement of appetite, was observed in some cases. Conclusion: Transdermal application of maropitant to cats experiencing vomiting seems to be efficient and a good alternative to existing oral medication, taking into account the difficulty of oral administration in these cases. This work provides preliminary clinical results of the efficacy of transdermal maropitant in cats. Further studies are necessary to determine dosing and pharmacokinetics.

Clinical Applications of Substance P (Neurokinin-1 Receptor) Antagonist in Canine Medicine.

Substance P binds to the Neurokinin-1 (NK-1) receptors found in the emetic center of the central nervous system (CNS) to induce emesis. Maropitant is a selective NK-1 receptor antagonist that inhibits the binding of substance P to NK-1 receptors and is commonly used to prevent and treat vomiting in dogs. This review study aimed to discuss and analyze the therapeutic potential of substance P (Neurokinin-1 receptor) antagonist with a particular focus on the drug maropitant in canine medicine. A systematic literature review was performed to identify the existing literature on the subject during the past 20 years (2001-2021) using such databases as ScienceDirect, PubMed, Scopus, and Google Scholar. The initial search identified 173 articles; however, 41 articles were selected for further analysis, based on the specific inclusion and exclusion criteria. Studies have already confirmed the role of substance P and NK-1 receptors in central pain processing, intestinal smooth muscle contraction, vasodilation, and neurogenic inflammation. Maropitant is one of the most effective veterinary antiemetic drugs that work well against peripheral and central stimuli that trigger the vomiting center. It has been already demonstrated that the therapeutic efficacy of maropitant for managing acute vomiting in dogs is associated with pancreatitis, gastritis, and parvoviral enteritis. It can also prevent and treat chemotherapy-induced emesis and delay the signs of nausea and adverse gastrointestinal effects. Regarding the broad-spectrum antiemetic activity of maropitant, it can be recommended for managing uremic vomiting in dogs. In addition, it has also exhibited an anesthetic sparing effect since the dogs treated with maropitant require a slightly lower percentage of isoflurane as an inhalational anesthetic. The NK-1 receptors are also identified in different areas of the pain pathways. Therefore, NK-1 receptor antagonists might be effective for managing visceral pain. However, further studies are required to establish the broad therapeutic potential of NK-1 receptor antagonist drugs, such as maropitant in canine medicine. It has been shown that the pain associated with the subcutaneous administration of maropitant is due to metacresol, a preservative used in some formulations. Therefore, the side effects can be eliminated by developing novel maropitant formulations specifically for dogs.

Effect of combinations of morphine, dexmedetomidine and maropitant on the electroencephalogram in response to acute electrical stimulation in anaesthetized dogs.

This study was conducted to compare the efficacy of combinations of morphine, dexmedetomidine and maropitant in preventing the changes in electroencephalographic (EEG) indices of nociception in anaesthetized dogs subjected to a noxious electrical stimulus. In a crossover study, eight healthy adult dogs were randomly allocated to four groups: Mor: morphine 0.6 mg/kg; Dex + Mor: morphine 0.3 mg/kg + dexmedetomidine 5 µg/kg; Maro + Mor: morphine 0.3 mg/kg + maropitant 1 mg/kg; and Dex + Maro + Mor: morphine 0.2 mg/kg + dexmedetomidine 3 µg/kg + maropitant 0.7 mg/kg. Following intramuscular administration of test drugs in a minimal anaesthesia model, a supramaximal electrical stimulus (50 V at 50 Hz for 2 s) was applied and the EEG data were recorded. There were significant increases (p < .05) in the poststimulus median frequency (F50) only in groups Mor and Maro + Mor. Dex + Mor group had a significantly lower change in F50 and F95 compared to all other treatment groups. There was no correlation of the changes in EEG frequencies with blood plasma concentration of the drugs during and after noxious stimulation. Combination of dexmedetomidine and morphine was most effective in abolishing the changes in EEG indices in response to a noxious stimulus indicating a supra-additive interaction between these two drugs.

Evaluating the anti-inflammatory and analgesic properties of maropitant: A systematic review and meta-analysis.

The neurotransmitter Substance P, and its neurokinin-1 receptor (NK-1R) are involved in the regulation of many pathophysiological processes including emesis, inflammation and nociceptive processing. This review provides a brief summary of the anti-inflammatory and analgesic properties of experimental NK-1R antagonists followed by a systematic review and meta-analysis on maropitant, the only NK-1R antagonist with a label indication for emesis in veterinary patients. There is very limited evidence based information on the putative clinical utilisation of maropitant for pain and inflammation. The aim of this systematic review and meta-analysis was to evaluate published reports on anti-inflammatory, analgesic and anaesthesia-sparing effects of maropitant. Medline, Pubmed, Science direct and Web of Science were searched to identify all published studies on maropitant, followed by a meta-analysis. Fourteen studies with 128 animals receiving maropitant and 127 controls met the inclusion criteria. Overall, maropitant had a significant inhalation anaesthetic-sparing effect (SMD -0.92, 95% CI -1.30, -0.54; P < 0.00001). However, treatment with maropitant had no effect on pain (SMD 0.06, 95% CI -0.37, 0.48; P = 0.80), or leukocyte cell infiltration in different inflammatory conditions (SMD -0.60, 95% CI -1.31, 0.11; P = 0.10). Based on all eligible studies for this review, it can be deduced that maropitant significantly reduced the minimum alveolar concentrations for isoflurane and sevoflurane for many different surgical procedures but it had no clearly proven effect on inflammation and pain.

Antiemetic effect of oral maropitant treatment before the administration of brimonidine ophthalmic solution in healthy cats.

OBJECTIVES: The aim of this study was to investigate the antiemetic, behavioural and physiological effects of oral maropitant treatment before the administration of brimonidine ophthalmic solution in healthy cats. METHODS: Five cats received oral maropitant 8 mg or no treatment (control) 18 h before the administration of one drop of brimonidine solution in both eyes. Each cat was administered each of the two treatments, with a washout period of 1 week. The incidence of emesis, retching, sialorrhoea and lip-licking after brimonidine administration was recorded, while behavioural and physiological parameters, including heart rate, mean blood pressure, respiratory frequency and rectal temperature, were recorded before and 0, 30, 60, 90, 120, 180 and 240 mins after brimonidine administration. RESULTS: Emesis and retching were not observed when maropitant was administered. However, 4/5 cats exhibited vomiting and retching in the absence of maropitant pretreatment. The incidence of emesis and retching after brimonidine administration was significantly lower in the treatment group than in the control group. Sialorrhoea occurred in one cat in the control group, while all cats showed lip-licking after brimonidine administration. There were no significant differences in the incidence of sialorrhoea and lip-licking between the two groups. Although behaviour scores were comparable between the two groups, those obtained during heart rate, mean blood pressure and respiratory frequency measurements were significantly lower than the baseline scores; this indicated a sedative effect after brimonidine administration. The heart rate and mean blood pressure significantly decreased after brimonidine administration in both groups, while there were no intergroup differences in the heart rate, mean blood pressure, respiratory frequency and rectal temperature. CONCLUSIONS AND RELEVANCE: Oral maropitant treatment before the administration of brimonidine ophthalmic solution in cats can alleviate emesis and retching without affecting the sedative effects of brimonidine and important physiological parameters.

Evaluation of analgesic interaction between morphine, dexmedetomidine and maropitant using hot-plate and tail-flick tests in rats.

OBJECTIVE: To determine if the combinations of morphine, dexmedetomidine and maropitant enhance the analgesic effect and decrease the dose of individual drugs in rats subjected to noxious thermal stimulation with hot-plate and tail-flick tests. STUDY DESIGN: Randomized, blinded, prospective experimental study. ANIMALS: A total of 96 male Sprague-Dawley rats. METHODS: The rats were randomly assigned to the following groups: 1) morphine (3 mg kg-1; Mor); 2) dexmedetomidine (10 µg kg-1; Dex); 3) maropitant (20 mg kg-1; Maro); 4) morphine (1.5 mg kg-1) + dexmedetomidine (5 µg kg-1; Mor + Dex); 5) dexmedetomidine (5 µg kg-1) + maropitant (10 mg kg-1; Dex + Maro); 6) morphine (1.5 mg kg-1) + maropitant (10 mg kg-1; Mor + Maro); 7) morphine (1 mg kg-1) + dexmedetomidine (3.5 µg kg-1) + maropitant (6.5 mg kg-1; Mor + Dex + Maro); and 8) normal saline (0.5 mL; saline), all injected intravenously. The tail-flick and hot-plate tests were performed before and 5, 15, 30, 45, 60, 90 and 120 minutes after the injection of the drugs. These variables were analysed with the effect-time area under the curve (AUC) analysis and a mixed linear model. RESULTS: Data were analysed in 94 rats. The rank order of the total analgesic effects of the treatment groups shown by AUC analysis was found to be Mor > Maro + Mor > Dex + Mor > Dex > Maro > Dex + Maro + Mor > Dex + Maro > saline for the hot-plate test, and Maro + Mor > Mor > Dex + Mor > Dex + Maro + Mor > Maro > Dex > Dex + Maro > saline for the tail-flick test. The mixed model analysis showed a significant difference between latencies of the group morphine + maropitant versus all other treatment groups in the tail-flick test (p < 0.0001) and morphine versus saline in the hot-plate test (p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Morphine and maropitant appeared to show a supra-additive effect for analgesia in the tail-flick test. Clinical trials should be conducted to establish its use in treating pain.

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.

Use of maropitant for the control of pruritus in non-flea, non-food-induced feline hypersensitivity dermatitis: an open-label, uncontrolled pilot study.

OBJECTIVES: Non-flea, non-food-induced hypersensitivity dermatitis (NFNFIHD) is a common inflammatory and pruritic skin disease in cats. When avoidance and conventional systemic immunosuppressive treatments fail to control the clinical signs, there are limited treatment options. The aim of this study was to evaluate the efficacy and tolerability of maropitant in feline NFNFIHD. METHODS: In an open-label, uncontrolled study, cats with proven non-seasonal NFNFIHD were treated with maropitant 2 mg/kg PO q24h for 4 weeks. Clinical lesions were evaluated with the Scoring Feline Allergic Dermatitis (SCORFAD) system and pruritus was evaluated with a 10 cm visual analogue scale (VAS) before and at the end of the study. Owners assessed global efficacy and tolerability with a 4-point scale at the end of the study. Adverse events and body weight changes were recorded. RESULTS: Twelve cats were treated with a mean initial maropitant dose of 2.22 mg/kg PO q24h. The treatment decreased both SCORFAD and pruritus VAS (pVAS) scores in all cats except one, in which only pruritus was reduced. The efficacy and the tolerability of the treatment were judged as excellent or good by 83.3% of owners. Treatment did not cause any side effects other than, in a few cases, short-time, self-limiting sialorrhoea. CONCLUSIONS AND RELEVANCE: Maropitant seems to be an effective, well-tolerated therapeutic option to control pruritus in cats. Caution is needed in interpreting the results as the pVAS score system has not yet been validated in cats and the trial was uncontrolled. A further, controlled study is required to confirm our findings.

Assessment of pre-operative maropitant citrate use in macaque (Macaca fasicularis & Macaca mulatta) neurosurgical procedures.

BACKGROUND: Retrospective analysis of post-operative vomiting (POV) in non-human primates at our institution was 11%. Based on this additional risk factor for post-operative complications, we aimed to eliminate or decrease POV by adding an antiemetic, maropitant citrate, to the pre-medication protocol. METHODS: Retrospective and prospective data were collected over a 5-year period from 46 macaques of two species during 155 procedures. Additionally, blood was collected from five Macaca mulatta to perform a pharmacokinetic analysis. RESULTS: A 1 mg/kg subcutaneous dose of maropitant given pre-operatively significantly decreased POV. Findings indicated post-neurosurgical emesis in Macaca fasicularis was significantly greater than in Macaca mulatta. Pharmacokinetic analysis of maropitant in Macaca mulatta determined the mean maximum plasma concentration to be 113 ng/mL. CONCLUSIONS: Maropitant administration prior to anesthesia for neurosurgeries decreased our incidence of POV to 1%. The plasma concentration reaches the proposed plasma level for clinical efficacy approximately 20 minutes after administration.

Comparison of pain response after subcutaneous injection of two maropitant formulations to beagle dogs.

The antiemetic maropitant, with metacresol as preservative (Cerenia, Zoetis), has been associated with pain after subcutaneous injection in dogs and cats. Recently, a generic formulation containing benzyl alcohol was authorised (Prevomax, Le Vet). Benzyl alcohol is reported to have local anaesthetic properties and reduce injection pain. This study compared local pain after subcutaneous injection of the two maropitant formulations, administered at approximately 4°C and 25°C, to dogs. Thirty-two healthy beagle dogs were enrolled into a blinded, randomised, cross-over study. Dogs received subcutaneous injections of maropitant injection containing metacresol as preservative and maropitant injection containing benzyl alcohol as preservative, both at approximately 4°C and 25°C, with at least three days in between treatments. Injection pain was evaluated by two blinded observers using a visual analogue scale immediately after injection and a simple descriptive scale at two minutes after injection. In healthy beagle dogs, subcutaneous injection of maropitant with benzyl alcohol is significantly less painful than injection of maropitant with metacresol.

The effect of maropitant on intraoperative isoflurane requirements and postoperative nausea and vomiting in dogs: a randomized clinical trial.

OBJECTIVE: To establish if preoperative maropitant significantly reduced intraoperative isoflurane requirements and reduced clinical signs associated with postoperative nausea and vomiting (PONV) in dogs. STUDY DESIGN: Randomized clinical trial. ANIMALS: Twenty-four healthy, client-owned dogs undergoing routine ovariohysterectomy. METHODS: Premedication involved acepromazine (0.03 mg kg-1) combined with methadone (0.3 mg kg-1) intramuscularly 45 minutes before anaesthetic induction with intravenous (IV) propofol, dosed to effect. Meloxicam (0.2 mg kg-1) was administered intravenously. Dogs were randomly assigned to administration of saline (group S; 0.1 mL kg-1, n=12) or maropitant (group M; 1 mg kg-1, n=12) subcutaneously at time of premedication. Methadone (0.1 mg kg-1 IV) was repeated 4 hours later. Anaesthesia was maintained with isoflurane in oxygen, dosed to effect by an observer unaware of group allocation. The dogs were assessed hourly, starting 1 hour postoperatively, using the short form of the Glasgow Composite Pain Score (GCPS), and for ptyalism and signs attributable to PONV [score from 0 (none) to 3 (severe)] by blinded observers. Owners completed a questionnaire at the postoperative recheck. RESULTS: Overall mean±standard deviation end-tidal isoflurane percentage was lower in group M (1.19±0.26%) than group S (1.44±0.23%) (p=0.022), but was not significantly different between groups at specific noxious events (skin incision, ovarian pedicle clamp application, cervical clamp application, wound closure). Cardiorespiratory variables and postoperative GCPS were not significantly different between groups. Overall, 50% of dogs displayed signs attributable to PONV, with no difference in PONV scores between groups (p=0.198). No difference in anaesthetic recovery was noted by owners between groups. CONCLUSIONS: Maropitant reduced overall intraoperative isoflurane requirements but did not affect the incidence of PONV. CLINICAL RELEVANCE: Maropitant provided no significant benefits to dogs undergoing ovariohysterectomy with this anaesthetic and analgesic protocol, although clinically significant reductions in isoflurane requirements were noted.

Anti-nausea effects and pharmacokinetics of ondansetron, maropitant and metoclopramide in a low-dose cisplatin model of nausea and vomiting in the dog: a blinded crossover study.

BACKGROUND: Nausea is a subjective sensation which is difficult to measure in non-verbal species. The aims of this study were to determine the efficacy of three classes of antiemetic drugs in a novel low dose cisplatin model of nausea and vomiting and measure change in potential nausea biomarkers arginine vasopressin (AVP) and cortisol. A four period cross-over blinded study was conducted in eight healthy beagle dogs of both genders. Dogs were administered 18 mg/m2 cisplatin intravenously, followed 45 min later by a 15 min infusion of either placebo (saline) or antiemetic treatment with ondansetron (0.5 mg/kg; 5-HT3 antagonist), maropitant (1 mg/kg; NK1 antagonist) or metoclopramide (0.5 mg/kg; D2 antagonist). The number of vomits and nausea associated behaviours, scored on a visual analogue scale, were recorded every 15 min for 8 h following cisplatin administration. Plasma samples were collected to measure AVP, cortisol and antiemetic drug concentrations. RESULTS: The placebo treated group vomited an average number of 7 times (range 2-13). None of the dogs in either the ondansetron or maropitant treated groups vomited during the observation period. The onset of nausea-like behaviour in the placebo-treated group occurred at t3.5h and peaked at t4.75h with nausea behaviour score of 58.5 ± 4.6 mm. Ondansetron and maropitant reduced overall the area under the curve of nausea behaviour score by 90% and 25%, respectively. Metoclopramide had no effect on either vomiting or nausea. Cisplatin-induced nausea and vomiting caused concomitant increases in AVP and cortisol. In the placebo-treated group, AVP and cortisol increased from t2.5h, peaked at t5h (11.3 ± 2.9 pmol L-1 and 334.0 ± 46.7 nmol/L, respectively) and returned to baseline by t8h. AVP and cortisol increases were completely prevented by ondansetron and only partially by maropitant, while metoclopramide had no effect. The terminal half-lives (harmonic mean ± pseudo SD) for ondansetron, maropitant and metoclopramide were 1.21 ± 0.51, 5.62 ± 0.77 and 0.87 ± 0.17 h respectively. CONCLUSIONS: 5-HT3 receptor antagonist ondansetron demonstrates the greatest anti-emetic and anti-nausea efficacy of the three drugs. AVP and cortisol appear to be selective biomarkers of nausea rather than emesis, providing a means of objectively measuring of nausea in the dog.

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.

Spotlight on the perioperative use of maropitant citrate.

Neurokinin-1 (NK-1) receptors are present in both the central nervous system and peripheral tissues. Substance P (SP) is the major ligand and is involved in multiple processes including pain transmission, vasodilation, modulation of the inflammatory response, as well as the sensory neuronal transmission involved in stress, anxiety, and emesis. The involvement of NK-1 and SP in the vomiting reflex has led to the development of NK-1 antagonists to prevent and treat vomiting in human and veterinary medicine. Maropitant is a potent, selective neurokinin (NK-1) receptor antagonist that blocks the pharmacologic action of SP in the central nervous system. Maropitant is available in both an injectable and tablet formulation and approved for use in dogs and cats for the treatment and prevention of vomiting from a variety of clinical causes and motion sickness. When administered prior to anesthetic premedication, maropitant prevents or significantly decreases the incidence of opioid-induced vomiting and signs of nausea in dogs and cats. Maropitant has also been shown to improve postoperative return to feeding and food intake in dogs. The minimum alveolar concentration of sevoflurage is decreased in both dogs and cats by maropitant, indicating a potential role as an adjunct analgesic, especially for visceral pain. This article will review the background information and literature, including clinical recommendations with respect to the perioperative use of maropitant in canine and feline veterinary patients.