Efficacy of the new anthelmintic drug Supramil® tablets in intestinal helminthiases of dogs and cats
V.A. Оrobets1, Grand PhD of Veterinary Sciences, professor, Head of Department of therapy and pharmacology (orobets@yandex.ru);
O.I. Sevostyanova1, Ph.D. in Biology Science, Senior Lecturer Department of therapy and pharmacology (sevostyanova19@mail.ru);
I.V. Zaichenko2, PhD in Veterinary Science, the chief veterinarian (igorzaichenko@mail.ru);
S.V. Mukaseev3, PhD in Veterinary Science, the veterinarian (mukaseev@aspect-ag.com);
O.A. Zeynalov4, PhD in Biology Science, chief science specialist.
1Federal State Budget Educational Institution of Higher Education "Stavropol Stae Agrarian University" (12, Zootechnical side-street, Stavropol, RF, 355017).
2Veterinary center "Na Pirogova" (24/2, Pirogova street, Stavropol, RF, 355045).
3LLC AG Aspect (ap. 6, build 3, h. 20, Nauchny pr, Moscow, RF, 117246).
4LLC RPC SKiFF (ap. 204, build 3, h. 20, Nauchny pr, Moscow, RF, 117246).
The effectiveness of a new anthelmintic drug for dogs and cats Supramil® tablets was studied. Therapeutic efficacy of the drug Supramil® tablets after a single application in dogs and puppies with spontaneous invasions of intestinal nematodes and/or cestodes at a dose of 2.5 mg/kg for R-praziquantel and 0.5 mg/kg for milbemycin oxime in toxocariasis, toxascariasis, ankylostomosis, trichuriasis , dipylidiosis, teniasis, mesocestoidosis, as well as with mixed nematode-cestodesis invasions was 100%.
Therapeutic efficacy of the drug Supramil® tablets after a single application in dogs and puppies with spontaneous invasions of intestinal nematodes and/or cestodes at a dose of 2.5 mg/kg for R-praziquantel and 2.0 mg/kg for milbemycin oxime in toxocariasis, ankylostomosis, trichuriasis, dipylidiosis, teniasis, and with mixed nematode-cestodesis invasions was 100%
Thus, Supramil® tablets are a highly effective for the most common intestinal helminthiases of dogs and cats
Keywords: efficacy, Supramil® tablets, R-praziquantel, milbemycin oxime, dogs, puppies, cats, kittens, intestinal nematodes, intestinal cestodes, mixed invasion.
The drug was developed and marketed under the sponsorship of Fund for the Promotion of the Development of Small Businesses in the Sphere of Science and Technology.
Abbreviations: AA — active agent(s), GIT— gastrointestinal tract, BW — body weight, EE— extensive efficiency, LD50 — lethal dose (half lethal dose)
Introduction
According to the study of animal food manufacturer Mars Petcare and Yandex.Market, the number of pets in Russia has increased by 14% since 2014. Today, 55 million Russian households have cats and dogs, with that 15% respondents have a cat and a dog. In our country there are almost twice as many cats than there are dogs: 33.7 and 18.9 million accordingly [28]. It is also important to note that recently pet owners became more responsible towards their pets, treating them as family members, that, among others, requires increased competence level of owners concerning veterinary care, including the aspects of invasion and infectious diseases.
Considering this, the problems connected with helminthiases of cats and dogs, which is one of the most common diseases and occur in different region of the Russian Federation all year round [5, 8, 11, 13, 25, 26], today does not lose its relevance. The above mentioned population growth of cats and dogs, including homeless ones, high reproductive capacity of helminthiases pathogens, long-term survival and saving invasion elements in the environment increase the spread of parasitosis and circulation of their pathogens both in cities and in rural areas [3, 6, 12, 24]. We should keep in mind, however, that particular danger is posed for humans by helminthozoonoses caused by pathogens that are general both for humans and animals, such as toxocariasis, ankylostomosis, echinococcosis, dirofilariasis, dipylidiosis and some other diseases [1, 2, 4, 7, 9, 10, 18, 21, 23].
Dehelmintization is the main measure against helminthiases. There is a great range of agents in various formula, widely traded in Russian veterinary market, used for anthelminthic treatments of cats and dogs. However, many of them do not fully meet the up-to-date requirements for applied AA, their efficiency, safety and availability for a pet owner. It demands development of new domestic anthelminthic drugs having enhanced pharmacotoxicological characteristics.
To accomplish this task in 2019 specialists of research and innovation company "Astrapharm" and research and production company "SKiFF" [17] developed a new anthelmintic drug Supramil® tablets, containing as AA the combination of R-praziquantel, an active optical isomer of praziquantel and milbemycin oxime.
Brief description of the new anthelmintic drug Supramil® tablets
Presentation
Supramil® tablets are presented in five modifications with different AA content in a tablet:
- "Supramil® tablets for cats and kittens up to 2 kg" (103 mg): R-praziquantel 2.5 mg and milbemycin oxime 2.0 mg, 1 tablet for 1.0 kg of BW;
- "Supramil® tablets for cats with weight from 2 kg" (103 mg): R-praziquantel 10.0 mg and milbemycin oxime 8.0 mg, 1 tablet for 4.0 kg of BW;
- "Supramil® tablets for puppies and dogs up to 5 kg" (103 mg): R-praziquantel 6.25 mg and milbemycin oxime 1.25 mg, 1 tablet for 2.5 kg of BW;
- "Supramil® tablets for puppies and dogs up to 20 kg" (103 mg): R-praziquantel 25.0 mg and milbemycin oxime 5.0 mg, 1 tablet for 10.0 kg of BW;
- "Supramil® tablets for dogs 20 to 50 kg" (309 mg): R-praziquantel — 62.5 mg and milbemycin oxime 12.5 mg, 1 tablet for 25.0 kg of BW;
- Supramil® tablets are presented in five modifications with different AA content in a tablet:
Active agents
R-praziquantel. Supramil® tablets are the world's second (after Prazitel® suspension Special [16, 20…22]) peroral anthelminthic containing R-praziquantel, an active levorotary isomer of praziquantel determining its cestodocidal action [31, 32, 34, 35, 37, 38].
Praziquantel, currently widely used in formulation of commercial medical and veterinary drugs for treatment of cestodeses (dipylidiosis, teniasis, echinococcosis, alveococcosis, diphyllobothriasis, mesocestoidiasis) and trematodiases (opisthorchiasis, schistosomiasis) contains equal proportions of R-praziquantel, a highly-active levorotary optical isomer, and S-praziquantel, a low-active dextrorotary optical isomer [29, 30, 34, 35]. The mechanism of action of the active enantiomer is based on the induction of tegument degradation, persistent depolarization of the helminth muscle cells, violation of energy exchange, which causes paralysis and death of cestodes and removes them from the gastrointestinal tract. R-praziquantel is quickly absorbed by the gastrointestinal tract, reaching the maximum concentration in blod plazma after 1-3 h, where it reversibly binds to blood serum proteins (70-80%). The compound is partially metabolized in liver, then re-excreted into the intestine and excreted from the body, mainly with urine (up to 80%) during 24 hours.
According to literature, acute toxicity of racemic praziquantel when administered to mice is characterised by LD50= 2500 mg/kg (III class of hazard according to GOST 12.1.007). Regarding acute toxicity data of R-praziquantel, by the time of development of Supramil® , there were no reliable information on this issue in the literature. In 2015, we first determined the LD50 of the R-praziquantel substance, which was 7925 mg/kg in mice when administered perorally (IV class of hazard according to GOST 12.1.007-76) [15].
Milbemycin oxime. It is a macrocyclic lactone derived from the enzymatic activity of Streptomyces hygroscopicus var. aureolacrimosus, active for lavrae and adults of nematodes, parasitizing in the gastrointestinal tract of cats and dogs, as well as lavrae of nematode Dirofilaria spp. The mechanism of action of milbemycin oxime is reasoned by increase of permeability of cell membranes for chloride ions (Сl- ), which leads to overpolarization of nervous and muscle tissue cell membranes, paralysis and death of sensitive nematodes. The maximum concentration of milbemycin oxime in blood plasma of dogs is reached during 2-4 h, of cats — within 2 h; bioavailability is about 80%. The compound is excreted from the body mainly in an unchanged form. The compound relates to III class of danger according to GOST 12.1.007- 76.
The combination of milbemycin oxime with praziquantel, represented by a racemic mixture, is quite actively used in veterinary practice, particularly, it is the basis of well-known foreign commercial preparations Milbemax (Elanco Europe Ltd, Great Britain) and Milprazone (KRKA, Slovenia). The drugs show a wide range of anthelmintic action and high efficiency against nematodes and some types of cestodes in cats and dogs. Certain disadvantages of the mentioned foreign analogues can be allocated III class of danger, as well as saved dose of cestodical component of 5 mg/kg traditionally used in the most veterinary anthelmintics. Use of active R-praziquantel instead of racemate in Supramil® formulation made it possible to reduce in half its dosage while maintaining 100% cestodocidal efficacy in a single use, which is confirmed by the results provided for in this paper and literature data [31, 33, 36, 39], as well as dramatically increase safety of the new anthelminthic for animals from III to IV class of danger according to GOST 12.1.007 [15] as compared with the closest foreign analogues.
Prescription and application
Supramil® tablets are prescribed to adult dogs and cats, puppies and kittens for therapeutic and prophylactic purposes once for intestinal nematodes induced by Ancylostoma caninum, Ancylostoma tubaeforme, Toxocara canis, Toxacara cati, Toxascaris leonina, Trichuris vulpis, cestodes, induced by Dipylidium caninum, Taenia spp., Mesocestoides spp., associated nematodecestodesis invasions and for dirofilariasis prevention
Palatability
The important aspect of efficiency of any peroral antihelminthic is how the animals sense its taste (palatability), which significantly influence on performance and efficiency of dehelmintization in whole.
Taking with in account, Supramil® tablets are additionally coated with a film with the flavoring. This not only makes the tablet more attractive for animals, but protects it from adverse effects of the environment.
Acceptability
Everyday application of the anthelmintic drug Supramil® tablets by dogs, puppies, cats and kittens for seven days in a dosage two-three times increasing recommended by the Instruction doesn't affect the general state of animals, their physiological status and behavior. No significant changes of morphological composition and biochemical parameters of blood of target animals were noted by statistics. The results of tolerance study confirm safety of drug administration in the recommended dose schedule.
This article presents experiment data received during study of efficiency of the anthelmintic drug Supramil® tablets at the most common nematodes and cestodes in cats and dogs and puppies and kittens as well.
Material and methods
Study of therapeutic efficiency of the anthelmintic drug Supramil® tablets at nematodes and cestodes in cats and dogs and puppies and kittens as well was carried out in 2019 on the basis of the Department of Therapy and Pharmacology of FSBEI HE Stavropol State Agrarian University, "Best Friend" animal shelter of Stavropol city, live-stock facilities Novomarevskoe, LLC, Temnolesskaya stanitsa and Tatarka village of Shpakovskiy district, Stavropol Region.
The study included adult outbred dogs of different age both male and female, puppies from 4-weeks old age, adult outbred cats of different age, both male and female and kittens from 6-weeks old age, infected with intestinal helminths. In total 163 adult dogs, 120 puppies, 123 adult cats and 42 kittens spontaneously infected intestinal nematodes and/or cestodes took part in the study.
The study of therapeutic efficiency of drugs Supramil® tablets included:
а) Supramil® tablets for puppies and dogs up to 5 kg— 41 dogs and 48 puppies, infected with Toxocara сanis (24 specimen), Toxascaris leonina (21 specimen), Dipylidium caninum (22 specimen) as well as with mixed invasion Toxocara canis + Dipylidium caninum (22 specimen);
b) Supramil® tablets for puppies and dogs up to 20 kg — 77 dogs and 72 puppies, infected with Toxocara сanis (27 specimen), Toxascaris leonina (23 specimen), Ancylostoma caninum (21 specimen), Trichuris vulpis (10 specimen), Dipylidium caninum (23 specimen), Taenia spp.(22 specimen), as well as with mixed invasion Ancylostoma caninum + Taenia spp. (12 specimen) and Trichuris vulpis + Taenia spp. (11 specimen);
c) Supramil® tablets for dogs 20…50 kg — 45 dogs with mixed invasion of Ancylostoma caninum+ Trichuris vulpis + Taenia spp. (12 specimen), Ancylostoma caninum + Taenia spp. (11 specimen) and Trichuris vulpis + Taenia spp. (11 specimen), as well as with infection of Mesocestoides spp. (11 specimen);
d) Supramil® tablets for kittens and cats up to 2 kg — 51 cats and 42 kittens, infected with Toxocara сati (22 specimen), Ancylostoma tubaeformae (21 specimen), Dipylidium caninum (20 specimen), Taenia spp. (10 specimen), as well as with mixed invasion Toxocara сati + Taenia spp. (20 specimen);
d) Supramil® tablets for cats over 2 kg— 72 cats, infected with Toxocara сati (11 specimen), Ancylostoma tubaeformae (11 specimen), Trichuris vulpis (10 specimen), Dipylidium caninum (10 specimen), Taenia spp. (10 specimen), and with mixed invasion as well Toxocara сati + Taenia spp. (10 specimen) and Trichuris vulpis + Taenia spp. (10 specimen).
The diagnosis of helminthiases was made based on coproovoscopic examination by McMaster method. Species membership of helminths was determined using an atlas [27]. After diagnosis was made, the animals were weighted and randomly divided into experimental and control groups according to body weight.
Animals of experimental groups were administered 2.5 mg R-praziquantel and 0.5 mg milbemycin perorally during morning feeding for 1 kg BW for dogs and 2.5 mg R-praziquantel and 2.0 mg milbemycin for 1 kg BW for cats, which in a preliminary experiment were defined as minimal therapeutic doses which give 100% efficiency of dehelmintization.
Many animal ate the drug on their own, the rest have no problems with taking tablets due to their small size and coating with a flavor. Animals of the control groups didn't receive the treatment.
Therapeutic efficiency of the anthelmintic drug Supramil® tablets was established by comparison of quantity of invasion elements of helminths in 1 g of feces before and after 10...14 days after dehelmintization of experimental groups of animals using EE index of treatment — number of animals (in percent of the number of treated ones), which were completely free from helminths and percent of reduction of helminth eggs number after treatment. The second index was determined for the animals of control groups. The obtained results were statistically processed using Microsoft Excel 2016 software.
The animals treated with the anthelmintic were constantly monitored to assess their clinical condition during administration of the anthelmintic drug Supramil® tablets.
Results
Therapeutic efficacy of the anthelmintic drug Supramil® tablets in intestinal helminthiases to dogs and puppies. In all studies on determination of the therapeutic efficiency, Supramil® tablets for dogs and puppies was used in the minimal therapeutic dose, which for R-praziquantel was 2.5 mg/kg of the animal body weight, for milbemycin oxime 0.5 mg/kg of body weight.
Obtained results are given in tables 1…8.
Data given in tables 1…3 refer to the study of modification of the drug intended for use in dogs and puppies up to 5 kg with the most common nematodosis (table 1), cestodosis (table 2) and mixed invasion (table 3). It obviously follows fromthe obtained results that after a single use of the recommended doses of antihelminthic drug Supramil® tablets for dogs and puppies to 5 kg after 10...14 days in all studied invasions, no helminths eggs in feces of the experimental animals were revealed; with that the determined index of the number reduction (100 %) is observed in all dogs, without exception, of the experimental groups, that is EE of treatment makes up 100 %.
The number of helminths eggs in feces of animals in control groups, determined in the same periods as of treated dogs, in the majority of cases either preserved at the initial level or increased.
Tables 4…6 give the results of study of Supramil® tablets efficiency for dogs and puppies weighing up to 20 kg, which was performed with the same method used for the first modification of the tableted antihekminthic, that is for treatment of the most common nematodosis (table 4), cestodosis (table 5) and mixed invasion (table 6). According to data received, efficiency of dehelmintization, as in the first part of the experiment, in all types of infection was 100% (EE index — 100 %; index of eggs number reduction — 100 %). There were no reduction of helminths eggs number in feces of the animals of control groups.
Tables 7 and 8 provide data obtained by using Supramil® tablets for dogs with BW up to 20 to 50 kg for dehelmintization of animals with the most common mixed (nematodosis, cestodosis) invasions (table 7), and mesocestoidiasis as well (table 8). It 4 • Russian Veterinary Journal • No. 2/2022 • is evident that use of the drug modification intended for large dogs subject to compliance with regulated doses and conditions of use in all cases will also provide 100% dehelmintization result.
In the course of performing study of the new drug on dogs, no deviation of animals's clinic state from the standard one was recorded.
Thus, the results of the new anthelminthic's efficiency examination on dogs and puppies allow to make the following conclusions:
a) Supramil® tablets for with a single administration in dogs and puppies infested with toxocara, ankylostomosis, trichuris, dipilidiums, taenia, mesocestoidiasis and mixed nematode-cestodesis invasion shows 100% EE and provides 100% reduction of invasion elements of nematodes and cestodesis after the treatment. b) dehelmintization of dogs and puppies with the new drug doesn't result in disorders of the clinical condition of the animals.
Therapeutic efficacy of the Supramil® tablets for cats and kittens in helminthiases. In the study of the therapeutic efficiency of the anthelmintic drug Supramil® tablets for cats and kittens, the minimal therapeutic dose of R-praziquantel was 2.5 mg/kg of body weight, for milbemycin oxime 2.0 mg/kg of body weight. The results of therapeutic efficiency of the drug in intestinal helminthiases of cats and kittens are given in tables 9…14.
1.Therapeutic efficacy of the Supramil® tablets for puppies and dogs up to 5 kg in intestinal nematodoses
| Animals | Number of animals in a group | Type of helminths | Number of infected animals | Average amount of helminth eggs in 1 g of feces | Reduction of eggs number after treatment, % | ||||
|---|---|---|---|---|---|---|---|---|---|
| before treatment | after treatment | EE, % | before treatmen | after treatment | |||||
| Experimental group | |||||||||
| Dogs | 5 | Toxocara сanis | 5 | 0 | 100.0 | 120.2±54.5 | 0.0 | 100.0 | |
| 5 | Toxascaris leonina | 5 | 0 | 100.0 | 354.2±89.6 | 0.0 | 100.0 | ||
| Puppies | 8 | Toxocara сanis | 8 | 0 | 100.0 | 458.1±151.2 | 0.0 | 100.0 | |
| 6 | Toxascaris leonina | 6 | 0 | 100.0 | 423.2±78.5 | 0.0 | 100.0 | ||
| Control group | |||||||||
| Dogs | 5 | Toxocara сanis | 5 | 5 | 0.0 | 68.4±11.3 | 99.4±65.2 | - | |
| 5 | Toxascaris leonina | 5 | 5 | 0.0 | 165.2±79.3 | 429.4±101.2 | - | ||
| Puppies | 6 | Toxocara сanis | 6 | 6 | 0.0 | 295.3±168.0 | 312.3±78.6 | - | |
| 5 | Toxascaris leonina | 5 | 5 | 0.0 | 265.8±64.0 | 329.6±98.7 | - | ||
2. Therapeutic efficacy of the Supramil® tablets for puppies and dogs up to 5 kg in dipilidiasis
| Animals | Number of animals in a group | Type of helminths | Number of infected animals | Average amount of helminth eggs in 1 g of feces | Reduction of eggs number after treatment, % | ||||
|---|---|---|---|---|---|---|---|---|---|
| before treatment | after treatment | EE, % | before treatmen | after treatment | |||||
| Experimental group | |||||||||
| Dogs | 6 | Dipylidium caninum | 6 | 0 | 100.0 | 370.3±109.1 | 0.0 | 100.0 | |
| Puppies | 6 | 6 | 0 | 100.0 | 368.5±76.9 | 0.0 | 100.0 | ||
| Control group | |||||||||
| Dogs | 5 | Dipylidium caninum | 5 | 5 | 0.0 | 241.2±66.2 | 168.8±71.8 | - | |
| Puppies | 5 | 5 | 5 | 0.0 | 132.4±46.8 | 132.4±46.8 | - | ||
3. Therapeutic efficacy of the Supramil® tablets for puppies and dogs up to 5 kg in mixed invasion
| Animals | Number of animals in a group | Type of helminths | Number of infected animals | Average amount of helminth eggs in 1 g of feces | Reduction of eggs number after treatment, % | |||
|---|---|---|---|---|---|---|---|---|
| before treatment | after treatment | EE, % | before treatmen | after treatment | ||||
| Dogs | 5 | Toxocara сanis | 5 | 0 | 100.0 | 163.2±41.8 | 0.0 | 100.0 |
| Dipylidium caninum | 5 | 0 | 100.0 | 292.6±88.6 | 0.0 | 100.0 | ||
| Puppies | 7 | Toxocara сanis | 7 | 0 | 100.0 | 568.9±133.1 | 0.0 | 100.0 |
| Dipylidium caninum | 7 | 0 | 100.0 | 357.7±52.2 | 0.0 | 100.0 | ||
| Control group | ||||||||
| Dogs | 5 | Toxocara сanis | 5 | 5 | 0.0 | 123.4±72.7 | 172.4±52.3 | - |
| Dipylidium caninum | 5 | 5 | 0.0 | 206.0±74.5 | 409.6±66.3 | - | ||
| Puppies | 5 | Toxocara сanis | 5 | 5 | 0.0 | 335.7±220.9 | 248.6±162.5 | - |
| Dipylidium caninum | 5 | 5 | 0.0 | 208.4±139 | 295.1±191.8 | - | ||
4. Therapeutic efficacy of the Supramil® tablets for puppies and dogs up to 20 kg in nematodоses
| Animals | Number of animals in a group | Type of helminths | Number of infected animals | Average amount of helminth eggs in 1 g of feces | Reduction of eggs number after treatment, % | |||
|---|---|---|---|---|---|---|---|---|
| before treatment | after treatment | EE, % | before treatmen | after treatment | ||||
| Experimental group | ||||||||
| Dogs | 7 | Toxocara сanis | 7 | 0 | 100.0 | 385.3±66.0 | 0.0 | 100.0 |
| 6 | Toxascaris leonina | 6 | 0 | 100.0 | 166.3±51.9 | 0.0 | 100.0 | |
| 5 | Ancylostoma caninum | 5 | 0 | 100.0 | 587.6±149.2 | 0.0 | 100.0 | |
| 5 | Trichuris vulpis | 5 | 0 | 100.0 | 180.8±82.6 | 0.0 | 100.0 | |
| Puppies | 9 | Toxocara сanis | 9 | 0 | 100.0 | 502.9±81.5 | 0.0 | 100.0 |
| 6 | Toxascaris leonina | 6 | 0 | 100.0 | 235.6±146.9 | 0.0 | 100.0 | |
| 6 | Ancylostoma caninum | 6 | 0 | 100.0 | 854.6±499.8 | 0.0 | 100.0 | |
| Control group | ||||||||
| Dogs | 5 | Toxocara сanis | 5 | 5 | 0.0 | 169.2±133.5 | 125.3±82.9 | - |
| 5 | Toxascaris leonina | 5 | 5 | 0.0 | 92.8±71.4 | 128.6±87.9 | - | |
| 5 | Ancylostoma caninum | 5 | 5 | 0.0 | 322.3±225.4 | 376.8±201.8 | - | |
| 5 | Trichuris vulpis | 5 | 5 | 0.0 | 112.4±84.4 | 87.7±49.5 | - | |
| Puppies | 6 | Toxocara сanis | 6 | 6 | 0.0 | 354.7±226.1 | 468.4±217.3 | - |
| 6 | Toxascaris leonina | 6 | 6 | 0.0 | 162.1±101.2 | 420.1±186.5 | - | |
| 5 | Ancylostoma caninum | 5 | 5 | 0.0 | 524.3±329.1 | 662.5±468.5 | - | |
5. Therapeutic efficacy of the Supramil® tablets for puppies and dogs up to 20 kg in cestodes
| Animals | Number of animals in a group | Type of helminths | Number of infected animals | Average amount of helminth eggs in 1 g of feces | Reduction of eggs number after treatment, % | |||
|---|---|---|---|---|---|---|---|---|
| before treatment | after treatment | EE, % | before treatmen | after treatment | ||||
| Experimental group | ||||||||
| Dogs |
7 | Dipylidium caninum | 7 | 0 | 100.0 | 356.7±174.3 | 0.0 | 100.0 |
| 6 | Taenia spp. | 6 | 0 | 100.0 | 187.4±121.6 | 0.0 | 100.0 | |
| Puppies |
6 | Dipylidium caninum | 6 | 0 | 100.0 | 435.3±263.8 | 0.0 | 100.0 |
| 6 | Taenia spp. | 6 | 0 | 100.0 | 292.8±171.6 | 0.0 | 100.0 | |
| Control group | ||||||||
| Dogs |
5 | Dipylidium caninum | 5 | 5 | 0.0 | 229.8±166.8 | 306.5±166.8 | - |
| 5 | Taenia spp. | 5 | 5 | 0.0 | 384.1±277.6 | 328.2±188.1 | - | |
| Puppies |
5 | Dipylidium caninum | 5 | 5 | 0.0 | 128.9±104.9 | 162.3±114.8 | - |
| 5 | Taenia spp. | 5 | 5 | 0.0 | 88.6±70.8 | 116.3±86.5 | - | |
6. Therapeutic efficacy of the Supramil® tablets for puppies and dogs up to 20 kg in mixed invasion
| Animals | Number of animals in a group | Type of helminths | Number of infected animals | Average amount of helminth eggs in 1 g of feces | Reduction of eggs number after treatment, % | |||
|---|---|---|---|---|---|---|---|---|
| before treatment | after treatment | EE, % | before treatmen | after treatment | ||||
| Experimental group | ||||||||
| Dogs | 6 | Trichuris vulpis | 6 | 0 | 100.0 | 66.7±40.7 | 0.0 | 100.0 |
| Taenia spp. | 6 | 0 | 100.0 | 358.8±192.6 | 0.0 | 100.0 | ||
| Puppies | 7 | Ancylostoma caninum | 7 | 0 | 100.0 | 782.1±354.2 | 0.0 | 100.0 |
| Taenia spp. | 7 | 0 | 100.0 | 358.3±52.4 | 0.0 | 100.0 | ||
| Control group | ||||||||
| Dogs | 5 | Trichuris vulpis | 5 | 5 | 0.0 | 148.7±117.5 | 178.3±126.3 | - |
| Taenia spp. | 5 | 5 | 0.0 | 228.2±176.1 | 269.3±177.1 | - | ||
| Puppies | 5 | Ancylostoma caninum | 5 | 5 | 0.0 | 458.8±343.5 | 552.6±365.0 | - |
| Taenia spp. | 5 | 5 | 0.0 | 178.1±131.5 | 228.3±146.2 | - | ||
Data given in tables 9…11 refer to the study of modification of the drug intended for use in cats and kittens with BW up to 2 kg with the most common nematodosis (table 9), cestodosis (table 10) and mixed invasion (table 11). From the results of the performed experiment follows that after 10...14 days after a single use of the recommended doses of antihelminthic drug Supramil® tablets for cats and kittens weighing up to 2 kg with primary intestinal helminthiases, no invasion elements in feces of the experimental animals were revealed; with that the determined index of the number reduction (100 %) is observed in all cats and kittens, without exception, of the experimental groups, that is EE of treatment makes up 100 %.
Number of helminths eggs in feces of animals in control groups, determined in the same periods as of treated cats and kittens, either preserved at the initial level or increased.
Tables 12…14 give the results of study of Supramil® tablets efficiency for cats weighing over 2 kg, which was performed with the same method used for the first modification of the anthelminthic, that is for treatment of nematodosis (table 12), cestodosis (table 13) and mixed invasion (table 14). According to data received, efficiency of dehelmintization in all types of infection was 100% (EE index — 100 %; index of eggs number reduction — 100 %). There was no reduction of helminths eggs number in the animals of control groups.
7. Therapeutic efficacy of the Supramil® tablets for dogs 20…50 kg in mixed invasion
| Animals | Number of animals in a group | Type of helminths | Number of infected animals | Average amount of helminth eggs in 1 g of feces | Reduction of eggs number after treatment, % | |||
|---|---|---|---|---|---|---|---|---|
| before treatment | after treatment | EE, % | before treatmen | after treatment | ||||
| Experimental group | ||||||||
| Dogs | 7 | Ancylostoma caninum Trichuris vulpis Taenia spp. |
7 7 7 |
0 0 0 |
100.0 100.0 100.0 |
698.3±307.2 148.7±33.9 358.8±176.1 |
0.0 0.0 0.0 |
100.0 100.0 100.0 |
| 6 | Ancylostoma caninum Taenia spp. |
6 6 |
0 0 |
100.0 100.0 |
456.3±278.3 146.6±68.9 |
0.0 0.0 |
100.0 100.0 |
|
| 6 | Trichuris vulpis Taenia spp. |
6 6 |
0 0 |
100.0 100.0 |
64.8±42.8 174.1±98.0 |
0.0 0.0 |
100.0 100.0 |
|
| Control group | ||||||||
| Dogs | 5 | Ancylostoma caninum Trichuris vulpis Taenia spp. |
5 5 5 |
5 5 5 |
0.0 0.0 0.0 |
440.7±310.8 134.5±99.5 364.3±261.5 |
551.7±294.5 105.2±56.9 286.3±156.8 |
- - - |
| 5 | Ancylostoma caninum Taenia spp. |
5 5 |
5 5 |
0.0 0.0 |
538.9±382.9 328.4±229.3 |
625.7±345.9 253.5±136.8 |
- - |
|
| 5 | Trichuris vulpis Taenia spp. |
5 5 |
5 5 |
0.0 0.0 |
176.5±129.5 324.4±227.2 |
142.2±81.9 288.2±159.7 |
- - |
|
8. Therapeutic efficacy of the Supramil® tablets for dogs 20…50 kg in mesocestoidiasis
| Animals | Number of animals in a group | Type of helminths | Number of infected animals | Average amount of helminth eggs in 1 g of feces | Reduction of eggs number after treatment, % | |||
|---|---|---|---|---|---|---|---|---|
| before treatment | after treatment | EE, % | before treatmen | after treatment | ||||
| Experimental group | ||||||||
| Dogs | 6 | Mesocestoides spp. | 6 | 0 | 100.0 | 184.2±113.4 | 0.0 | 100.0 |
| Control group | ||||||||
| Dogs | 5 | Mesocestoides spp. | 5 | 5 | 0.0 | 190.2±150.9 | 159.4±111.3 | - |
9. Therapeutic efficacy of the Supramil® tablets for kittens and cats up to 2 kg in intestinal nematodoses
| Animals | Number of animals in a group | Type of helminths | Number of infected animals | Average amount of helminth eggs in 1 g of feces | Reduction of eggs number after treatment, % | |||
|---|---|---|---|---|---|---|---|---|
| before treatment | after treatment | EE, % | before treatmen | after treatment | ||||
| Experimental group | ||||||||
| Cats |
6 | Toxocara сati | 6 | 0 | 100.0 | 128.5±37.6 | 0.0 | 100.0 |
| 5 | Ancylostoma tubaeforme | 5 | 0 | 100.0 | 445.6±102.3 | 0.0 | 100.0 | |
| Kittens |
6 | Toxocara сati | 6 | 0 | 100.0 | 368.2±74.6 | 0.0 | 100.0 |
| 6 | Ancylostoma tubaeforme | 6 | 0 | 100.0 | 687.8±114.9 | 0.0 | 100.0 | |
| Control group | ||||||||
| Cats |
5 | Toxocara сati | 5 | 5 | 0.0 | 98.8±67.6 | 168.5±121.4 | - |
| 5 | Ancylostoma tubaeforme | 5 | 5 | 0.0 | 349.5±195.8 | 284.3±149.1 | - | |
| Kittens |
5 | Toxocara сati | 5 | 5 | 0.0 | 354.2±203.5 | 268.8±144.7 | - |
| 5 | Ancylostoma tubaeforme | 5 | 5 | 0.0 | 572.2±303.3 | 428.7±228.4 | - | |
10. Therapeutic efficacy of the Supramil® ablets for kittens and cats up to 2 kg in cestodoses
| Animals | Number of animals in a group | Type of helminths | Number of infected animals | Average amount of helminth eggs in 1 g of feces | Reduction of eggs number after treatment, % | |||
|---|---|---|---|---|---|---|---|---|
| before treatment | after treatment | EE, % | before treatmen | after treatment | ||||
| Experimental group | ||||||||
| Cats |
6 | Toxocara сati | 6 | 0 | 100.0 | 128.5±37.6 | 0.0 | 100.0 |
| 5 | Ancylostoma tubaeforme | 5 | 0 | 100.0 | 445.6±102.3 | 0.0 | 100.0 | |
| Kittens |
6 | Toxocara сati | 6 | 0 | 100.0 | 368.2±74.6 | 0.0 | 100.0 |
| 6 | Ancylostoma tubaeforme | 6 | 0 | 100.0 | 687.8±114.9 | 0.0 | 100.0 | |
| Control group | ||||||||
| Cats |
5 | Toxocara сati | 5 | 5 | 0.0 | 98.8±67.6 | 168.5±121.4 | - |
| 5 | Ancylostoma tubaeforme | 5 | 5 | 0.0 | 349.5±195.8 | 284.3±149.1 | - | |
| Kittens |
5 | Toxocara сati | 5 | 5 | 0.0 | 354.2±203.5 | 268.8±144.7 | - |
| 5 | Ancylostoma tubaeforme | 5 | 5 | 0.0 | 572.2±303.3 | 428.7±228.4 | - | |
11. Therapeutic efficacy of the Supramil® tablets for kittens and cats up to 2 kg in mixed invasion
| Animals | Number of animals in a group | Type of helminths | Number of infected animals | Average amount of helminth eggs in 1 g of feces | Reduction of eggs number after treatment, % | |||
|---|---|---|---|---|---|---|---|---|
| before treatment | after treatment | EE, % | before treatmen | after treatment | ||||
| Experimental group | ||||||||
| Cats |
5 |
Toxocara сati | 5 | 0 | 100.0 | 658.3±347.9 | 0.0 | 100.0 |
| Taenia spp. | 5 | 0 | 100.0 | 120.2±77.8 | 0.0 | 100.0 | ||
| Kittens | 5 | Toxocara сati | 5 | 0 | 100.0 | 427.7±206.3 | 0.0 | 100.0 |
| Taenia spp. | 5 | 0 | 100.0 | 99.3±55.4 | 0.0 | 100.0 | ||
| Control group | ||||||||
| Cats | 5 | Toxocara сati | 5 | 5 | 0.0 | 382.2±203.3 | 320.3±174.1 | - |
| Taenia spp. | 5 | 5 | 0.0 | 136.7±83.0 | 112.5±65.8 | - | ||
| Kittens | 5 | Toxocara сati | 5 | 5 | 0.0 | 523.8±272.3 | 486.5±254.7 | - |
| Taenia spp. | 5 | 5 | 0.0 | 80.7±48.4 | 114.3±62.0 | - | ||
12. Therapeutic efficacy of the Supramil® tablets for cats over 2 kg in intestinal nematodoses
| Animals | Number of animals in a group | Type of helminths | Number of infected animals | Average amount of helminth eggs in 1 g of feces | Reduction of eggs number after treatment, % | |||
|---|---|---|---|---|---|---|---|---|
| before treatment | after treatment | EE, % | before treatmen | after treatment | ||||
| Experimental group | ||||||||
| Cats |
6 | Toxocara сati | 6 | 0 | 100.0 | 352.7±65.3 | 0.0 | 100.0 |
| 6 | Ancylostoma tubaeforme | 6 | 0 | 100.0 | 684.8±132.9 | 0.0 | 100.0 | |
| 5 | Trichuris vulpis | 5 | 0 | 100.0 | 66.4±23.7 | 0.0 | 100.0 | |
| Control group | ||||||||
| Cats |
5 | Toxocara сati | 5 | 5 | 0.0 | 239.6±64.8 | 364.2±43.4 | - |
| 5 | Ancylostoma tubaeforme | 5 | 5 | 0.0 | 458.2±73.3 | 527.6±77.9 | - | |
| 5 | Trichuris vulpis | 5 | 5 | 0.0 | 82.4±14.7 | 102.4±26.8 | - | |
13. Therapeutic efficacy of the Supramil® tablets for cats over 2 kg in intestinal cestodoses
| Animals | Number of animals in a group | Type of helminths | Number of infected animals | Average amount of helminth eggs in 1 g of feces | Reduction of eggs number after treatment, % | |||
|---|---|---|---|---|---|---|---|---|
| before treatment | after treatment | EE, % | before treatmen | after treatment | ||||
| Experimental group | ||||||||
| Cats |
5 | Dipylidium caninum | 5 | 0 | 100.0 | 98.2±31.7 | 0.0 | 100.0 |
| 5 | Taenia spp. | 5 | 0 | 100.0 | 124.4±32.6 | 0.0 | 100.0 | |
| Control group | ||||||||
| Cats |
5 | Dipylidium caninum | 5 | 5 | 0.0 | 64.8±29.7 | 116.6±28.4 | - |
| 5 | Taenia spp. | 5 | 5 | 0.0 | 63.6±26.2 | 109.2±20.1 | - | |
14. Therapeutic efficacy of the Supramil® tablets for cats over 2 kg in mixed invasion
| Animals | Number of animals in a group | Type of helminths | Number of infected animals | Average amount of helminth eggs in 1 g of feces | Reduction of eggs number after treatment, % | |||
|---|---|---|---|---|---|---|---|---|
| before treatment | after treatment | EE, % | before treatmen | after treatment | ||||
| Experimental group | ||||||||
| Cats |
5 |
Toxocara сati Taenia spp. | 5 5 | 0 0 | 100.0 100.0 | 469.6±138.2 230.8±96.5 | 0 0 | 100 100 |
| 5 |
Trichuris vulpis Taenia spp. | 5 5 | 0 0 | 100.0 100.0 | 225.6±92.9 192.4±133.9 | 0 0 | 100 100 | |
| Control group | ||||||||
| Cats |
5 |
Toxocara сati Taenia spp. | 5 5 | 5 5 | 0.0 0.0 | 305.4±64.2 194.6±116.3 | 348.2±84.5 228.6±104.5 | - - |
| 5 |
Trichuris vulpis Taenia spp. | 5 5 | 5 5 | 0.0 0.0 | 194.4±71.1 168.6±73.6 | 211.4±58.7 226.4±84.7 | - - | |
In the course of performing study of the drug on cats and kittens, no deviation of animals's clinic state from the standard one was recorded.
Thus, the results of the new anthelminthic's efficiency examination on cats and kittens allow to make the following conclusions.
a) Supramil® tablets for cats and kittens with a single administration, spontaneously infested with toxocara, ankylostomosis, trichuris, dipilidiums, taenia and mixed nematode-cestodesis invasion shows 100% extensive efficiency and provides 100% reduction of invasion elements of nematodes and cestodesis after treatment.
b) dehelmintization of cats and kittens with the new drug doesn't result in disorders of the clinical condition of the animals.
Conclusion
By the specialists of "Astrafarm" and research and production company "SKiFF" developed combined anthelmintic drug Supramil® tablets for cats and dogs for treating nematodes, cestodes, mixed invasions of cats and dogs, as well as dirofilariasis prevention. The drug contains R-praziquantel and milbemycin oxime as an active agent. By the degree of influence on the body, Supramil® tablets fall under the category of low-hazard substances and well tolerated by animals of different age groups when used in recommended doses.
Therapeutic efficacy of the antihelminthic drug Supramil® tablets after a single application in dogs and puppies with spontaneous invasions of intestinal nematodes and/or cestodes at a dose of 2.5 mg/kg for R-praziquantel and 0.5 mg/kg for milbemycin oxime in toxocariasis, toxascariasis, ankylostomosis, trichuriasis, dipylidiosis, teniasis, mesocestoidiasis and with mixed nematode-cestodesis invasions was 100%.
Therapeutic efficacy of the antihelminthic drug Supramil® tablets after a single application in cats and kittens with spontaneous invasions of intestinal nematodes and/or cestodes at a dose of 2.5 mg/kg for R-praziquantel and 2.0 mg/kg for milbemycin oxime in toxocariasis, ankylostomosis, trichuriasis, dipylidiosis, teniasis, and with mixed nematode-cestodesis invasions was 100%.
Supramil® tablets are coated with a film with a beef flavor. This made it possible to increase flavor of the tablet for animals, mask taste and odor of AA, neutralizing all possible negative reactions to the drug administered, facilitates swallowing and improves aesthetic characteristics of the tablet.
The drug has equal efficiency, when the specified therapeutic doses are complied with, for animals of different age (dogs and puppies, cats and kittens) and doesn't make any adverse effect on their clinical condition.
Thus, Supramil® tablets are a highly effective and safe means for treatment the most common intestinal helminthiases of dogs and cats.
Conflict of interests
The manufacturer of Supramil® tablets and sponsor of this study are RIC Astrapharm and LLC RPC SKiFF. The decision to publish the results of scientific work belongs to the developers.
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