A blinded, randomized and controlled multicenter field study investigating the safety and efficacy of long-term use of enflicoxib in the treatment of naturally occurring osteoarthritis in client-owned dogs.

Background: Enflicoxib is a COX-2 selective NSAID shown to be efficacious and safe in the treatment of pain and inflammation associated with canine osteoarthritis (OA) in clinical studies of 6 weeks duration. Objective: This prospective, multisite, blinded, randomized, placebo-controlled, parallel-group field study aimed to confirm the safety and efficacy of enflicoxib in long-term canine OA treatments. Animals: A total of 109 client owned dogs with clinical and radiographic signs of OA for at least 3 weeks were enrolled with 78 dogs completing all study visits. Methods: Dogs were randomized at a 3:1 ratio to receive enflicoxib (n = 83) or placebo (n = 26) once weekly during 6 months. Dogs underwent veterinary assessments from Day 0 to Day 189 using a clinical sum score (CSS). Efficacy was also assessed by the owners using the Canine Brief Pain Inventory (CBPI). Safety was assessed clinically and by repeated blood and urine sample analysis. The efficacy outcome measure was the treatment response according to the CSS and secondarily the treatment response according to the CBPI. The primary safety outcome was the incidence of adverse events (AEs) and secondarily the evolution of the clinical pathology parameters. Results: Percentages of CSS responders for enflicoxib were 71.6; 74.6 and 71.6% on Days 44, 135 and 189 respectively, always showing statistically significant differences (p < 0.05) vs. placebo (41.7, 33.3, and 20.8% respectively). Treatment response according to owner assessments followed the same pattern, achieving significant differences compared to placebo after 2 weeks of treatment. The incidence and type of AEs were as described in previous enflicoxib studies of shorter duration and as for other NSAIDs, with no tendency to increase over time. No relevant changes in hematology, biochemistry or urine parameters were observed. Conclusions and clinical relevance: Enflicoxib safety and efficacy profile is maintained after a long-term treatment, which together with its weekly administration, makes it a good alternative for the chronic treatment of dogs with naturally occurring OA.

A blinded, randomized and controlled multicenter clinical trial to assess the efficacy and safety of Leisguard® as an immunotherapeutic treatment for healthy Leishmania infantum-seropositive dogs.

BACKGROUND: Domperidone (Leisguard®) is an immunomodulatory drug used as a preventive measure in healthy dogs. However, no studies have been published in healthy Leishmania infantum-seropositive dogs. The aim of this study was to evaluate the clinical efficacy and safety of domperidone as immunotherapy in Leishmania-seropositive healthy dogs. METHODS: Sixty-seven dogs were treated with domperidone at 0.5 mg/kg and 44 dogs received placebo, once daily for 4 consecutive weeks. Monthly treatments were repeated every 4 months until the end of the 1-year follow-up period. Veterinary examinations were performed on days 0, 30, 120, 150, 240, 270 and 360. Samples of blood and urine were collected on days 0, 120, 240 and 360 for routine laboratory tests and quantitative in-house ELISA for the detection of L. infantum-specific antibodies. Furthermore, Leishmania real-time PCR and IFN-γ ELISA were performed at day 0 and the end of the study. Dogs that developed disease were withdrawn from the study and classified as sick dogs. Adverse drug reactions were reported. RESULTS: Thirty dogs developed disease during the follow-up period: 13/67 (19.4%) in the group treated with domperidone and 17/44 (38.6%) in the placebo-treated group (P = 0.03). Low-seropositive dogs treated with domperidone (4/40, 9.1%) were significantly less likely to develop disease compared to low-seropositive dogs treated with placebo (7/24, 29.2%; P = 0.04), while no differences were found between domperidone (9/23, 39.1%) and placebo (10/20, 50%) in medium- to high-seropositive dogs. At the end of the study, a higher proportion of Leishmania PCR-positive dogs was observed in the placebo-treated group (16/33, 48.5%) compared to the domperidone group (13/51, 25.5%; P = 0.04). Furthermore, low-seropositive dogs treated with domperidone with an increase of IFN-γ concentration presented a higher increase than those treated with placebo at the end of the study. Four dogs treated with domperidone presented self-limiting diarrhea. CONCLUSIONS: Healthy dogs with low L. infantum antibody levels treated with domperidone were less likely to develop disease compared to placebo-treated dogs. Furthermore, domperidone presented a good safety profile.

Enflicoxib for canine osteoarthritis: A randomized, blind, multicentre, non-inferiority clinical trial compared to mavacoxib.

BACKGROUND: This prospective, multisite, blinded, randomized, non-inferiority clinical study aimed to confirm the efficacy and safety of enflicoxib in the treatment of pain and inflammation associated with canine osteoarthritis. A total of 180 dogs were randomized to receive enflicoxib (n = 78), mavacoxib (n = 80) or placebo (n = 22). Dogs underwent veterinary assessments from day 0 to day 42 using a clinical sum score (CSS). Efficacy was also assessed by the owners using the Canine Brief Pain Inventory (CBPI). The primary efficacy endpoint was the overall CSS from day 0 to day 42. RESULTS: The overall CSS expressed as area under the curve demonstrated non-inferiority of enflicoxib compared to mavacoxib, and both showed superiority over placebo. At the end of the study, average CSS, and the percentage of CSS responders for enflicoxib (3.64 and 74%) and mavacoxib (4.49 and 68%), was superior to placebo (7.15 and 29%). A faster onset of action was observed for enflicoxib as superiority over placebo was evidenced from the first efficacy assessment (day 7) onwards for both parameters, whereas mavacoxib was only significantly different from day 14 onwards. According to the owner assessment, the percentage of CBPI responders was 90%, 79%, and 43% for dogs treated with enflicoxib, mavacoxib and placebo, respectively, and superiority over placebo was demonstrated for both active treatments. In all secondary parameters, non-inferiority of enflicoxib versus mavacoxib was confirmed. The dog's quality of life improved in all groups, but only enflicoxib showed superiority versus placebo. When assessing severely affected dogs only, results were similar, thus confirming the efficacy of enflicoxib in all stages of canine OA. There were no differences between groups in the frequency of adverse events, which were most frequently mild affecting the gastrointestinal tract and recovered without treatment. CONCLUSIONS: Enflicoxib is efficacious and safe for the treatment of pain and inflammation in any stage of canine osteoarthritis with a faster onset of action compared to mavacoxib.

Use of preventive measures and serological screening tools for Leishmania infantum infection in dogs from Europe.

BACKGROUND: There are several screening tools for detecting Leishmania infantum infection in dogs and various preventive measures to protect against it. Some studies have investigated them, but not many have described their current use. The aim of this study was to investigate which preventive measures and serological screening tools for L. infantum infection were employed from 2012 to 2018 in dogs from different endemic European countries. METHODS: A set of electronic datasheets was completed for each dog from several veterinary centres. Classification of preventive measures included: (1) repellents, (2) vaccines and (3) immunomodulators. Classification of serological tests included the: (1) direct agglutination test (DAT), (2) enzyme-linked immunosorbent assay (ELISA), (3) indirect immunofluorescence (IFI), (4) rapid tests and (5) other assays. Dogs were also classified depending on their risk of exposure and living area. RESULTS: Information from 3762 dogs was gathered. Preventive measures were applied in 91.5% of dogs and the most frequently used were repellents (86.2%) followed by vaccines (39.8%) and Leisguard® (15.3%). The different types of repellents (collar and spot-on) were used similarly. A combination of a vaccine and repellents was preferred in the high-risk group while the low-risk preferred a combination of Leisguard® and a repellent (Chi-square test: X2 = 88.41, df = 10, P < 0.001). Furthermore, all preventive measures were similarly used through the years except for repellents, which were predicted to have a small increase of use each year. Regarding serological screening tools, the most used were rapid and ELISA tests. Rapid tests, ELISA tests and DAT were used similarly through the years, but a significant change was found in the use of IFI and other assays whose use decreased a little each year. CONCLUSIONS: Repellents were the preferred measure, while vaccines and Leisguard® were second-line options. Some dogs were not treated by any measures, which highlights the need for dog owner education. Moreover, there seems to be a preference for rapid tests in the clinical setting to detect specific L. infantum antibodies while ELISA or IFI are less often employed. This underlines an increasing problem, as qualitative rapid tests have a variable diagnostic performance limiting the adequate diagnosis of seropositive dogs in endemic areas.

Evaluation of the Genotoxic Potential of the Selective COX-2 Inhibitor Enflicoxib in a Battery of in vitro and in vivo Genotoxicity Assays.

AIM: Enflicoxib, a selective COX-2 inhibitor approved for the treatment of pain and inflammation associated with osteoarthritis in dogs (Daxocox® [Ecuphar/Animalcare Group]) was assessed for its genotoxic potential in a battery of in vitro and in vivo genotoxicity assays. These comprised a bacterial reverse mutation assay (Ames test), an in vitro human lymphocyte chromosome aberration assay and an in vivo mouse bone marrow micronucleus assay. METHODS: Relevant vehicle and positive control cultures and animals were included in all assays. In the Ames test, enflicoxib was tested at concentrations of up to 5000 µg/plate. Signs of cytotoxicity were observed at the highest tested concentrations for several of the bacterial strains, both in absence and presence of S9. In human lymphocytes, enflicoxib was assessed for the induction of chromosomal aberrations when exposed at concentrations of up to 62.5 (3 hours) and 29.6 µg/mL (20 hours) in the absence of S9, and up to 66.7 µg/mL (3 hours) in presence of S9. Signs of cell toxicity, evidenced as a decrease in the mitotic index, were observed at these concentrations. In the mouse micronucleus assay, enflicoxib dose levels of up to 2000 mg/kg were administered (single dose) to male and female animals, and bone marrow samples were taken 24 and 48 hours (high-dose animals only) after administration. RESULTS: Enflicoxib was shown to lack genotoxic activity in the conducted assays. CONCLUSIONS: The administration of enflicoxib as a therapeutic analgesic agent would not pose a genotoxic risk to animals or humans.

Selective inhibition of cyclooxygenase-2 by enflicoxib, its enantiomers and its main metabolites in vitro in canine blood.

Enflicoxib is approved for the treatment of pain and inflammation in canine osteoarthritis. The objective of this work was to assess the mechanistic basis of enflicoxib therapy investigating the COX inhibitory activity of enflicoxib (racemate), its enantiomers and its main metabolites using the canine whole blood assay. The (R)-(+)-Enflicoxib enantiomer and metabolite M8 (hydroxylated pyrazoline) did not induce significant COX inhibition. Enflicoxib and its (S)-(-)-Enflicoxib enantiomer inhibited COX-1 and COX-2 with variable degree of preferential isoform inhibition, but no significant therapeutic effect is anticipated in vivo. The pyrazol metabolite showed the highest COX-2 inhibition and was the most selective (IC50 COX-1/ COX-2 ratio: 19.45). As the pyrazol metabolite shows saturable binding to red blood cells, its in vivo concentrations in plasma are lower than in whole blood. Accordingly, when applying the red blood cell partitioning, the respective IC50 and IC80 for COX-2 inhibition decreased from 2.8 µM (1129 ng/ml) and 13.4 µM (5404 ng/ml) to 0.2 µM (80.7 ng/ml) and 1.2 µM (484 ng/ml) and the selectivity ratio increased to close to 55. The corrected pyrazol metabolite IC50 and IC80 are well within the plasma levels described in treated dogs.

Pharmacology of enflicoxib, a new coxib drug: Efficacy and dose determination by clinical and pharmacokinetic-guided approach for the treatment of osteoarthritis in dogs based on an acute arthritis induction model.

Enflicoxib is a newly developed NSAID of the coxib class. The optimal therapeutic dose to be confirmed in the field studies was established using a combination of pharmacokinetic (PK) modelling and pharmacodynamic (PD) studies. First, a PK study was performed to determine the plasmatic profile of enflicoxib and its active pyrazol metabolite in dogs. Thereafter, two studies using a urate crystal-induced acute arthritis model allowed to correlate efficacy with plasmatic concentrations. Finally, a population PK model was developed to establish the Minimum Effective Concentration (MEC) and the Maximum Tolerated Concentration (MTC). Enflicoxib plasma concentrations were highest for the first 48 h. Thereafter, pyrazol metabolite concentrations were higher and persisted up to the end of the study. No reduction on the lameness (CLS) or pain scores (PS) was observed in the first hours after enflicoxib administration so no MEC could be established for the parent compound. Both CLS and PS were greatly reduced when the pyrazol metabolite achieved concentrations of 411 ng/ml or higher, so this concentration was established as the MEC for the pyrazol metabolite. Enflicoxib MTC was established at 6723 ng/ml whereas for the pyrazol metabolite it was 4258 ng/ml. The population PK model showed that a loading enflicoxib dose of 8 mg/kg followed by weekly maintenance doses of 4 mg/kg would achieve stable concentrations of the pyrazol metabolite within the therapeutic window (between the MEC and the MTC), and it was considered the most adequate posology to be confirmed in the field clinical studies for the treatment of canine osteoarthritis.

Efficacy and safety of enflicoxib for treatment of canine osteoarthritis: A 6-week randomised, controlled, blind, multicentre clinical trial.

BACKGROUND: Enflicoxib is a new COX-2 selective NSAID intended for the treatment of pain and inflammation associated with canine osteoarthritis. METHODS: A prospective, multisite, blinded, randomised, controlled, parallel-group field study was performed to determine the efficacy and safety of enflicoxib in canine osteoarthritis. A total of 242 dogs were randomised to receive enflicoxib at 4 or 2 mg/kg, mavacoxib at 2 mg/kg or placebo, orally. Enflicoxib and placebo were administered once weekly from day 0 to day 35. Mavacoxib was administered on D0 and day 14. Veterinarians assessed efficacy with a numerical rating scale and owners used the Canine Brief Pain Inventory. RESULTS: After 6 weeks, enflicoxib at 4 mg/kg showed the highest percentage of responders as assessed by the veterinarians (68%) and the owners (84%), followed by mavacoxib (62and 83%, respectively), and enflicoxib at 2 mg/kg (57 and 80%, respectively). All treatments reached statistical significance versus placebo, which obtained success rates of 37% and 53%, respectively. No differences in the incidence of adverse reactions were detected among the different groups. CONCLUSIONS: Enflicoxib administered weekly for 6 weeks, at 4 mg/kg PO with an initial loading dose of 8 mg/kg, is efficacious and safe for the treatment of canine osteoarthritis.

Comparative In vitro Metabolism of Enflicoxib in Dogs, Rats, and Humans: Main Metabolites and Proposed Metabolic Pathways.

BACKGROUND: Enflicoxib is a non-steroidal anti-inflammatory drug of the coxib family characterized by a long-lasting pharmacological activity that has been attributed to its active metabolite E-6132. OBJECTIVES: The aim of this work was to explore enflicoxib biotransformation In vitro in humans, rats and dogs, and to determine its metabolic pathways. METHODS: Different In vitro test systems were used, including hepatocytes and liver and non-hepatic microsomes. The samples were incubated with enflicoxib and/or any of its metabolites at 37°C for different times depending on the test system. The analyses were performed by liquid chromatography coupled with either radioactivity detection or high-resolution mass spectrometry. RESULTS: Enflicoxib was efficiently metabolized by cytochrome P-450 into three main phase I metabolites: M8, E-6132, and M7. The non-active hydroxy-pyrazoline metabolite M8 accounted for most of the fraction metabolized in all the three species. The active pyrazol metabolite E-6132 showed a slow formation rate, especially in dogs, whereas metabolite M7 was a secondary metabolite formed by oxidation of M8. In hepatocytes, diverse phase II metabolite conjugates were formed, including enflicoxib glucuronide, M8 glucuronide, E-6132 glucuronide, M7 glucuronide, and M7 sulfate. Metabolite E-6132 was most probably eliminated by a unique glucuronidation reaction at a very low rate. CONCLUSION: The phase I metabolism of enflicoxib was qualitatively very similar among rats, humans and dogs. The low formation and glucuronidation rates of the active enflicoxib metabolite E-6132 in dogs are postulated as key factors underlying the mechanism of its long-lasting pharmacokinetics and enflicoxib's overall sustained efficacy.

Long-term safety evaluation of Daxocox® tablets (enflicoxib) in dogs after weekly oral administrations for seven months.

BACKGROUND: Daxocox® [Ecuphar/Animalcare Group] contains the selective COX-2 inhibitor enflicoxib, approved in the EU for the treatment of pain and inflammation associated with osteoarthritis in dogs. The safety of Daxocox® was evaluated in a target animal safety study: Groups of 4 dogs per sex each were treated once weekly with placebo or Daxocox tablets at 1-, 3- and 5-times (1X, 3X and 5X) the maximum recommended therapeutic dose of enflicoxib (0, 4, 12 or 20 mg/kg, respectively). After an initial loading dose, dogs in the placebo control, 1X and 3X groups were administered for 32 weeks, and those in the 5X group were administered for 13 weeks. Dogs were subjected to daily food consumption measurements and clinical and dose observations. Body weight measurements, physical examinations, clinical pathology, urinalysis, faecal occult blood (FOB) and electrocardiographic (ECG) and blood pressure measurements, buccal mucosal bleeding time (BMBT), ophthalmology and gastroduodenal endoscopy examinations were conducted throughout the study. At study completion, all dogs were subjected to gross necropsy. Histopathology was performed on selected tissues from all animals in all groups. RESULTS: No clinical signs were noted, and no toxicologically relevant dose-associated effects were observed. CONCLUSIONS: Results show that Daxocox® is well-tolerated and has a broad safety margin when administered as directed in dogs.

Pharmacokinetics of enflicoxib in dogs: Effects of prandial state and repeated administration.

The pharmacokinetics of enflicoxib were evaluated in both a bioavailability study and a multi-dose safety study in Beagle dogs. When administered at 8 mg/kg, the oral bioavailability (F) of enflicoxib was 44.1% in fasted dogs, but F increased to 63.4% under post prandial conditions. Enflicoxib is rapidly metabolised. After the first 48 h, the plasma levels of its pyrazol metabolite were much higher and persistent than those of the parent compound. Following intravenous administration, the total body plasma clearance of enflicoxib was of 140 ml/h/kg and the volume of distribution based on the terminal phase was 4 L/kg. Plasma protein binding for both compounds was approximately 99%. The blood to plasma ratio for the pyrazol metabolite showed saturable kinetics with higher blood cell affinity at lower total blood concentrations which ranged from 2.49 to 0.95 for concentrations from 1 to 15 µg/ml. Enflicoxib and its pyrazol metabolite exhibited dose-proportional pharmacokinetics for single oral doses of 8-40 mg/kg and for multiple oral doses of 4-20 mg/kg. After 7 months of repeated weekly administrations, pre-dose plasma concentrations (Cmin,ss ) remained constant throughout the study, with no trend to any significant over-accumulation. The mean terminal elimination half-life (t½ ) was 20 h for enflicoxib and 17 days for the pyrazol metabolite. The pharmacokinetic profile of enflicoxib and its pyrazol metabolite in dogs supports the proposed dosing regimen in which doses are separated by 1 week.

Comparison of efficacy and safety of preventive measures used against canine leishmaniasis in southern European countries: Longitudinal retrospective study in 1647 client-owned dogs (2012-2016).

The best preventive strategy for canine leishmaniasis is, to date, unknown. In the last few years, new preventive measures have become available in Europe, including vaccination against leishmaniasis and the use of domperidone. The objective of the present study was to evaluate the efficacy and safety of the different preventive measures available against leishmaniasis in client-owned dogs. A database search of medical records was carried out in 52 private veterinary practices located in endemic areas of canine leishmaniasis in Spain, Italy and Portugal. Healthy seronegative dogs were included in the study. Serology was repeated at least 6 months later, and was used to retrospectively classify dogs into healthy, infected or sick. A total of 1647 dogs were included in the study. The use of preventive measures in this population was widespread. The single most utilized measure was repellents alone in 45.7% of dogs, followed by the combination of repellents and vaccination in 23.0%, repellents and domperidone in 11.3%, vaccination alone in 4.2%, vaccination and domperidone in 2.7%, domperidone alone in 2.3%, and the combination of the three measures in 0.2% of dogs. No preventive measure was applied in 10.7% dogs. The incidence of clinical leishmaniasis in the group with no preventive treatment applied was 12.5%. In the groups where prevention was applied, the reported incidence was the following: 10.1% for the vaccination only group, 4.5% for repellents only group, 4.0% for repellents + vaccination group, and 0.5% for repellents + domperidone group. No dogs in the groups of domperidone, vaccination + domperidone, and combination of the three measures developed clinical leishmaniasis. All preventive measures resulted in a significantly lower incidence of leishmaniasis compared to not applying any measure, except for vaccination alone. The majority of preventive strategies used, with exception of vaccination alone, decreased the incidence of leishmaniasis significantly. Adverse events, mild and self-limiting in most of the cases, were reported in 5.2% of dogs and were significantly more common in dogs following vaccination. In conclusion, this is the first large-scale field study investigating the efficacy and safety of the preventive measures used routinely against leishmaniasis in client-owned dogs. Most preventive strategies used, with exception of vaccination alone, had some benefit over not applying any preventive. In this field study, the use of repellents showed a good degree of protection in dogs living in endemic areas of canine leishmaniasis. Although lower numbers of dogs are included, the use of domperidone appeared to provide additional protection. The role of vaccination and its combination with other preventive strategies needs further study.

Effect of ketoprofen on pre-weaning piglet mortality on commercial farms.

The effect of ketoprofen on pre-weaning piglet mortality was evaluated in a large-scale study on commercial farms. Sows (n= 1486) from 15 farms were included. Half of the sows received 3 mg/kg ketoprofen in a single intramuscular administration within 12 h after farrowing. The other half remained untreated. Pre-weaning mortality was lower in the ketoprofen-treated group than in the control group (8.43% vs. 10.24%, respectively; P= 0.010). The major impact of ketoprofen on mortality was seen between days 2 and 7 postpartum (mortality rates of 2.75% vs. 4.02% for treated and control groups, respectively; P= 0.001). In addition, ketoprofen treatment was associated with a higher number of piglets weaned per litter than when no treatment was given (10.0 vs. 9.84, respectively; P= 0.012).

A single-centre, open-label, controlled, randomized clinical trial to assess the preventive efficacy of a domperidone-based treatment programme against clinical canine leishmaniasis in a high prevalence area.

The innate immune response acting immediately after initial infection with Leishmania parasites is known to play a relevant role in prevention against clinical progression of the disease. Domperidone is a dopamine D2 receptor antagonist that has shown to enhance the innate cell-mediated immune response. The aim of this study was to assess the preventive efficacy of a domperidone-based treatment programme against clinical canine leishmaniasis (CanL) in a high prevalence area. The study was performed with 90 healthy, seronegative dogs of different sex, age, weight and breed from a single veterinary clinic located in Valencia (Spain). Dogs were randomly allocated into two groups. Dogs in one group (domperidone-treated group; n=44) were administered an oral suspension of domperidone at 0.5 mg/kg bw/day during 30 consecutive days, every 4 months. Dogs in the other group (negative control group; n=46) were left untreated. A 21-month follow-up period was implemented covering two seasonal phases of the sand fly vector. During this period all animals underwent periodic clinical examinations and blood samplings for anti-Leishmania serological testing. Dogs seropositive for Leishmania (IFAT antibody titre≥1:80) plus at least one clinical sign consistent with CanL (indicative of active infection and incipient disease progression) were categorized as a 'prevention failure'. These dogs were withdrawn from the study after confirming the infection by direct observation of the parasite in smears of lymph nodes and/or bone marrow aspirates. The cumulative percentage of 'prevention failure' after 12 months was significantly lower in the domperidone-treated group than in the negative control group (7% versus 35%, p=0.003). Differences between groups persisted after 21 months (11% versus 48%, p<0.001). The prevention rate provided by domperidone was 80% during the first 12 months and 77% throughout the complete 21-month follow-up period, with odds ratios of 7.3 (p=0.001) and 7.15 (p<0.001), respectively, this indicating that the risk for domperidone-treated dogs to develop the clinical disease is quite 7 times lower than for dogs left untreated. The results of this study demonstrate that the implementation of a strategic domperidone-based treatment programme consisting in quarterly repeated 30-day treatments with domperidone effectively reduces the risk to develop clinical CanL in areas with high prevalence of the disease.

Use of the nitroblue tetrazolium reduction test for the evaluation of Domperidone effects on the neutrophilic function of healthy dogs.

The nitroblue tetrazolium reduction test (NBT) is an assay based on the activation percentage of neutrophils in peripheral blood, that has been proposed for the follow up of canine leishmaniosis owing to the narrow relationship between the molecules involved in the oxidative burst and the leishmanicidal activity of phagocytes. Domperidone is a drug used for the treatment of canine leishmaniosis having been claimed to stimulate the dogs' cell-mediated immune response. The aim of this study was to evaluate the degree and the lasting of phagocytic activation induced by a 30-day course treatment with Domperidone (0.5 mg/kg/day) in healthy dogs, by using the NBT. A statistically significant increase in the percentages of activated phagocytes was observed in the treated group during treatment, thereafter remaining high for up to one month after the end of treatment. In contrast, untreated dogs maintained the baseline percentage of activated neutrophils all along the study. It is concluded that the NBT is a useful tool for the follow up of the stimulating effects of Domperidone on the neutrophilic response of healthy dogs and that these effects persist for up to one month after treatment with this molecule.