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Evaluation of the Tolerance and Toxicity of an Oral Suspension on the

base of Triclabendazole, Ivermectin and Fenbendazole (Triverfen®22.2)*
in Calves**

José Fernando Tang Ploog, Jorge Fabián Ruiz Herrera, Luis Alberto Rodríguez Izaguirre***
______________________________________________________________________________________

Summary

The purpose of this study was to determine the maximum tolerated dose of the
active components of Triverfen 22.2 in twelve (12) 3-month-old Holstein cattle from a
dairy farm located in the department of Lima, these animals were divided in two
experimental groups to evaluate the possible toxic effects of the product Triverfen
22.2 in overdose. Group A received a single oral dose of 25 times the corresponding
therapeutic dose of Triverfen 22.2, while Group B received another single oral dose
of 50 times the corresponding therapeutic dose of Triverfen 22.2. Subsequently, said
animals were evaluated at 1 hour, 2 hours and 24 hours post application. The results
obtained for both groups demonstrated a high tolerance of the product Triverfen
22.2 orally,
_______________________________________________________________________________________

Abstract

The present study aimed at determining the maximum dose tolerated of the active components of
Triverfen 22.2 in twelve (12) Holstein breed cattle 3 months of age from a stable of dairy located in the
department of Lima, these animals were divided into two experimental groups to Assess the potential
toxic effects of the product Triverfen 22.2 in overdose. Group A received a single oral dose of 25 times the
therapeutic dose corresponding Triverfen 22.2, while Group B received another single oral dose of 50
times the therapeutic dose Triverfen 22.2. Subsequently these animals were evaluated at 1 hour, 2 hours
and 24 hours after application. The results for both groups showed a high tolerance of the product
Triverfen 22.2 orally, concluded up to 50 times the recommended therapeutic dose did not produce
adverse effects on the animals.
_______________________________________________________________________________________

1. INTRODUCTION For this reason, toxicity tests exist

and are carried out, through acute
Determining the toxicity of a toxicity studies, to establish the lethal
substance is important in order to doses for each route of administration.
establish the amount or concentration to
which it can be exposed to an organism. The lethal dose is that concentration
Some substances have, with small or dose of a substance or radiation that is
amounts, a positive effect on the body fatal for the animals that were
and become dangerous when taken in participants in the test. Lethal dose
higher concentrations. values are often used as a general
indicator of the acute toxicity of

* Triverfen®22.2is an antiparasitic oral suspension based on Triclabendazole 120 mg, Ivermectin 2 mg, Fenbendazole 100 mg
* * Study carried out in October 2008
*** MV Jose Fernando Tang Plog. Technical Manager – Agrovet Market SA
MV Jorge Fabian Ruiz Herrera. Head of Field Research and Evaluation – Agrovet Market SA
MV Luis Alberto Rodríguez Izaguirre. Field Research and Evaluation Assistant – Agrovet Market SA
A substance. It is generally expressed in mg of You get that you can be administered up to 83
toxic substance per kg of animal weight, and times of triclabendazole.
the most common is that the data is
accompanied by the animal in which it was For the case ofFenbendazole
tested (rats, rabbits, etc.). Reports indicate that up to 150 times
the therapeutic dose can be used in the
These lethal doses are classified as: case of cattle, while for other species
lethal dose 100 (LD100), that which such as sheep, pigs and horses (foals) it
causes the death of 100% of the animals can be dosed up to 125, 1000, 13 times
studied, lethal dose 50 (LD50), that which respectively the corresponding
causes the death of 50% of the animals, therapeutic dose.
and the maximum tolerated dose. (DLo),
which allows the survival of all animals. Toxic effects are observed in cattle
and sheep at a dose of 8 mg/Kg of
The purpose of this evaluation is to ivermectinwith clinical signs associated
determine the maximum tolerated dose with emesis in addition to ataxia,
of the active components of theTriverfen depression, mydriasis, polypnea, and
22.2based on the therapeutic doses of its muscle tremor. Knowing that the dose
active ingredients in bovine species, used is 0.2 mg / Kg, it is obtained that up
these being 12 mg/Kg of live weight for to 40 times its dose can be administered.
Triclabendazole for the most serious
cases of parasitism, 10 mg/Kg of live
weight for Fenbendazole and 200 2. OBJECTIVE
micrograms/ Kg live weight for
Ivermectin. Assess the Tolerance via the
oral administration of the product
For this reason, up to 50 times the Triverfen 22.2based on Triclabendazole
therapeutic dose will be evaluated as the 120mg, Fenbendazole 100mg and
maximum recommended limit for the Ivermectin 2mg per 1ml of suspension.
product. Triverfen 22.2, relying on Also determine the levels of toxicity on
various reports of maximum limits of the bovine species.
toxicity, described by various authors in
various species.
3. MATERIALS AND METHODS
As indicated by the studies carried
out and published by the OIE, where the Place of study:
triclabendazoleIt shows a very wide
range of tolerance, with the lethal dose The present study was carried out in
for sheep being 1000 mg/Kg/day, a dairy farm located in the town of
producing death in 100% of the animals Pachacamac, 31 km south of Lima,
at this concentration. Knowing that the located in the province of Lima,
dose of triclabendazole in cattle is 12 mg/ department of Lima, at an altitude of 200
Kg and considering that the lethal dose in masl and with an average environmental
sheep (ruminants) is 1000 mg/Kg, it is temperature of 12ºC.

* Triverfen®22.2is an antiparasitic oral suspension based on Triclabendazole 120 mg, Ivermectin 2 mg, Fenbendazole 100 mg
* * Study carried out in October 2008
*** MV Jose Fernando Tang Plog. Technical Manager – Agrovet Market SA
MV Jorge Fabian Ruiz Herrera. Head of Field Research and Evaluation – Agrovet Market SA
MV Luis Alberto Rodríguez Izaguirre. Field Research and Evaluation Assistant – Agrovet Market SA
Materials: Fenbendazole, equivalent to 50 times the respective
therapeutic dose for each active ingredient.
Twelve (12) 3-month-old Holstein
cattle, intensively reared in Subsequently, said animals were
stables, fed on a diet based on evaluated again at 1 hour, 2 hours and 24
green and concentrated forage. hours post application.

Antiparasitic oral suspension based on

Triclabendazole, Ivermectin and 4. RESULTS AND CONCLUSIONS
Fenbendazole(Triverfen®22.2).
The results obtained for both
Dosing gun. groups demonstrated a high tolerance
of the product.Triverfen 22.2orally,
Marker pen. being able to determine that up to 50
times the recommended therapeutic
Individual identification earrings and dose does not produce adverse effects
aretador. on the animals within 24 hours of
applying it.
Development of the Study:
The constants physiological
Twelve (12) cattle from stables were they remained within expectations,
selected, which were evaluated before likewise there were no digestive
the application of the product, with the alterations of any kind in the test
parameters to be evaluated being animals.
temperature, pulse, and respiratory rate.
Subsequently, the animals were weighed
and identified with earrings. 5. CONCLUSIONS

Then these cattle were divided into two It is concluded thatTriverfen 22.2it can
experimental groups to evaluate possible be administered up to 50 times the
toxic effects of the product.Triverfen 22.2 therapeutic dose without toxicity, as
in overdose. demonstrated by the studies carried out.

Group Areceived a single oral dose of 300

mg/kg of body weight of Triclabendazole, 6. BIBLIOGRAPHY
5,000 ug/kg of body weight of ivermectin and
250 mg/kg of body weight of Fenbendazole, 1.Blood, Henderson. Medicine
equivalent to 25 times the respective Vet. 5th Edition. Editorial
therapeutic dose for each active ingredient. Interamerican. Mexico 1986.

Group Breceived a single oral dose of 600 2. Snack.Veterinary Pharmacology and

mg/kg of body weight of Triclabendazole, Therapeutics. 1st Edition. 2002.
10,000 ug/kg of body weight of ivermectin and
500 mg/kg of body weight of

* Triverfen®22.2is an antiparasitic oral suspension based on Triclabendazole 120 mg, Ivermectin 2 mg, Fenbendazole 100 mg
* * Study carried out in October 2008
*** MV Jose Fernando Tang Plog. Technical Manager – Agrovet Market SA
MV Jorge Fabian Ruiz Herrera. Head of Field Research and Evaluation – Agrovet Market SA
MV Luis Alberto Rodríguez Izaguirre. Field Research and Evaluation Assistant – Agrovet Market SA
3. The Merck Veterinary Manual.5th http://www.rr-
Edition in Spanish. Ocean Publishing americas.oie.int/es/projects/Camevet/fic
Group. Barcelona, Spain. 2000. has/es_fichas_pharmacos.htm

4. Morales, Gustavo; Pino, Luz A.; 6. Rojas C., Marcelo.Nosoparasitosis of

Sandoval, Spartacus; Jimenez, Peruvian Domestic Ruminants. 2nd
Delia. Gastrointestinal helminthosis Edition. Lima Peru. 2004.
of cattle in Venezuela. Digital
Magazine of the National Center for 7. Sumano, Ocampo. Pharmacology
Agricultural Research of Vet. Second Edition.1998
Venezuela CENIAP. August 8. May –
number. 2005. in: 8. Veterinary Vademecum.Grupo Latino
http://www.ceniap.gov.ve/ceniaphoy/artic Editores Ltda. Colombia .2007.
ulos/n8/arti/morales_g2/morales_g2.htm
9. Veterinary Drug Handbook.4th Edition.
5. OIE.World organization for animal pocket edition. United States of America.
health. Registration form for . 2002.
pharmacological products for
veterinary use

* Triverfen®22.2is an antiparasitic oral suspension based on Triclabendazole 120 mg, Ivermectin 2 mg, Fenbendazole 100 mg
* * Study carried out in October 2008
*** MV Jose Fernando Tang Plog. Technical Manager – Agrovet Market SA
MV Jorge Fabian Ruiz Herrera. Head of Field Research and Evaluation – Agrovet Market SA
MV Luis Alberto Rodríguez Izaguirre. Field Research and Evaluation Assistant – Agrovet Market SA
 Table 01. Evaluation of Group A before the application of Triverfen®22.2

Age Frequency Frequency

No. Name Weight Temperature
(months) cardiac respiratory
1 Pike 3 75 80 38.3 28
2 Parakeet 3 70 88 38.9 28
3 White 2 70 60 38.2 30
4 Bull 3 65 72 38.5 32
5 Urpy 3 70 68 38.9 28
6 May 2.5 75 72 38.8 30

Table 02. Evaluation of Group B before the application of Triverfen®22.2

Age Frequency Frequency

No. Name Weight Temperature
(months) cardiac respiratory
1 Victor 2 65 60 37.9 30
2 Rambo 2.5 70 72 38.5 32
3 Queen 3 75 76 39.1 30
4 daddy 3 70 80 38.6 28
5 Sarah 2 75 72 39 30
6 lolo 3 65 64 38.5 32

* Triverfen®22.2is an antiparasitic oral suspension based on Triclabendazole 120 mg, Ivermectin 2 mg, Fenbendazole 100 mg
* * Study carried out in October 2008
*** MV Jose Fernando Tang Plog. Technical Manager – Agrovet Market SA
MV Jorge Fabian Ruiz Herrera. Head of Field Research and Evaluation – Agrovet Market SA
MV Luis Alberto Rodríguez Izaguirre. Field Research and Evaluation Assistant – Agrovet Market SA
 Table 03. Evaluation of Group A 1 hour Post-application of Triverfen®22.2

Age Dose Frequency Frequency

No. Name Weight Temperature
(months) (ml) cardiac respiratory
1 Pike 3 75 187.5 84 38.0 30
2 Parakeet 3 70 175 76 38.5 28
3 White 2 70 175 80 39.0 26
4 Bull 3 65 162.5 72 38.1 30
5 Urpy 3 70 175 76 38.5 32
6 May 2.5 75 187.5 80 38.9 30

Table 04. Evaluation of Group B 1 hour Post-application of Triverfen®22.2

Age Dose Frequency Frequency

No. Name Weight Temperature
(months) (ml) cardiac respiratory
1 Victor 2 65 325 90 37.1 32
2 Rambo 2.5 70 350 80 37.9 28
3 Queen 3 75 375 72 38.2 30
4 daddy 3 70 350 76 38.1 32
5 Sarah 2 75 375 72 38.3 30
6 lolo 3 65 325 80 38.5 28

* Triverfen®22.2is an antiparasitic oral suspension based on Triclabendazole 120 mg, Ivermectin 2 mg, Fenbendazole 100 mg
* * Study carried out in October 2008
*** MV Jose Fernando Tang Plog. Technical Manager – Agrovet Market SA
MV Jorge Fabian Ruiz Herrera. Head of Field Research and Evaluation – Agrovet Market SA
MV Luis Alberto Rodríguez Izaguirre. Field Research and Evaluation Assistant – Agrovet Market SA
 Table 05. Evaluation of Group A 24 hours Post-application of Triverfen®22.2

Age Dose Frequency Frequency

No. Name Weight Temperature
(months) (ml) cardiac respiratory
1 Pike 3 75 187.5 84 39.3 30
2 Parakeet 3 70 175 80 38.2 28
3 White 2 70 175 88 38.7 28
4 Bull 3 65 162.5 76 38.5 30
5 Urpy 3 70 175 72 38.2 28
6 May 2.5 75 187.5 76 38.6 32

Table 06. Evaluation of Group B 24 hours Post-application of Triverfen®22.2

Age Dose Frequency Frequency

No. Name Weight Temperature
(months) (ml) cardiac respiratory
1 Victor 2 65 325 76 38.3 28
2 Rambo 2.5 70 350 76 39.1 30
3 Queen 3 75 375 80 38.9 30
4 daddy 3 70 350 80 38.4 30
5 Sarah 2 75 375 72 38.3 30
6 lolo 3 65 325 84 38.8 32

* Triverfen®22.2is an antiparasitic oral suspension based on Triclabendazole 120 mg, Ivermectin 2 mg, Fenbendazole 100 mg
* * Study carried out in October 2008
*** MV Jose Fernando Tang Plog. Technical Manager – Agrovet Market SA
MV Jorge Fabian Ruiz Herrera. Head of Field Research and Evaluation – Agrovet Market SA
MV Luis Alberto Rodríguez Izaguirre. Field Research and Evaluation Assistant – Agrovet Market SA
 ATTACHED PHOTOS

Photo 1:Test animals Group A (25 times Therapeutic dose)

Photo 2:Test animals Group B (50 times Therapeutic dose)

* Triverfen®22.2is an antiparasitic oral suspension based on Triclabendazole 120 mg, Ivermectin 2 mg, Fenbendazole 100 mg
* * Study carried out in October 2008
*** MV Jose Fernando Tang Plog. Technical Manager – Agrovet Market SA
MV Jorge Fabian Ruiz Herrera. Head of Field Research and Evaluation – Agrovet Market SA
MV Luis Alberto Rodríguez Izaguirre. Field Research and Evaluation Assistant – Agrovet Market SA
 Photo 3: Dosage Group A Photo 4:Dosage Group A

* Triverfen®22.2is an antiparasitic oral suspension based on Triclabendazole 120 mg, Ivermectin 2 mg, Fenbendazole 100 mg
* * Study carried out in October 2008
*** MV Jose Fernando Tang Plog. Technical Manager – Agrovet Market SA
MV Jorge Fabian Ruiz Herrera. Head of Field Research and Evaluation – Agrovet Market SA
MV Luis Alberto Rodríguez Izaguirre. Field Research and Evaluation Assistant – Agrovet Market SA
 Photo 5:Dosage Group B

* Triverfen®22.2is an antiparasitic oral suspension based on Triclabendazole 120 mg, Ivermectin 2 mg, Fenbendazole 100 mg
* * Study carried out in October 2008
*** MV Jose Fernando Tang Plog. Technical Manager – Agrovet Market SA
MV Jorge Fabian Ruiz Herrera. Head of Field Research and Evaluation – Agrovet Market SA
MV Luis Alberto Rodríguez Izaguirre. Field Research and Evaluation Assistant – Agrovet Market SA