COCCIVEX

Coccibal

COCCIVEX
Amprolium 20% oral solution

> 40-years Summary

Amprolium is a thiamine-similar molecule, synthesized in 1962.

During many years it has been used
additive.

(with or without ethopabate) as

feed

In 2001, the authorization as feed additive, was withdrawn.

but

Amprolium was classified as anticoccidial drug, regulated by
EMEA and listed in Annex II

The EU regulations on the preventive use of in-feed coccidiostats
underwent a constant change.

Vaccination against coccidiosis became more popular.
Amprolium remained in the shadow of the prevention programs.
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COCCIVEX
Amprolium 20% oral solution

Despite the vaccination to boost immunity and shuttle programs
to reduce the risk of resistance to the in-feed coccidiostats,
clinical cases of coccidiosis still appear, in a lesser degree,
but not non-important.

Such coccidiosis outbreaks conducted to the need of an
anticoccidial tool, safe, easy and quickly available for use
at the farm unit.

Amprolium, anticoccidial API for oral use through drinking water,
acquired again importance, this time as veterinary drug to be used
in case of urgent anticoccidial treatment.

Its ban as in-feed coccidiostat favoured the decrease of

resistant Eimeria strains, becoming again effective as
anticoccidial for treatment.

Coccidiosis
Coccidiosis is a parasitic disease that can cause
severe losses in poultry meat and egg production.
The parasites multiply in the intestines and cause
tissue damage, lowered feed intake, poor absorption
of nutrients from the feed, dehydration, and blood
loss.
Birds are also more likely to get sick from secondary
bacterial infections.

Coccidiosis
Clinical disease occurs only after ingestion of
relatively large numbers of sporulated oocysts by
susceptible birds.
Both clinically infected and recovered birds shed
oocysts in their droppings, which contaminate feed,
dust, water, litter, and soil.
Fresh oocysts are not infective until they sporulate;
under optimal conditions [21-32C] with adequate
moisture and oxygen), this requires 1-2 days.
Sporulated oocysts may survive for long periods,
depending on environmental factors. Oocysts are
resistant to some disinfectants commonly used
around livestock but are killed by freezing or high
environmental temperatures.

Coccidiosis

Prepatent period: 4-7 days

- E acervulina: 5 d.

- E. maxima: 7 d.

- E. tenella: 7 d.

- E. brunetti: 6 d

- E. necatrix: 7 d.

- E. mitis

- E. praecox: 4 d.

Coccidiosis
Pathogenicity is influenced by host genetics,
nutritional factors, concurrent diseases, and species
of the coccidium.
Eimeria necatrix and E tenella are the most
pathogenic in chickens because schizogony occurs
in the lamina propria and crypts of Lieberkhn of the
small intestine and ceca, respectively, and causes
extensive hemorrhage.
Most species develop in epithelial cells lining the villi.
Protective immunity usually develops in response to
moderate and continuing infection.
Older birds are usually more resistant than young
birds because of earlier exposure to infection.

Coccidiosis
Eimeria
acervulina

E. tenella

E. maxima

E. mitis

E. necatrix

E. praecox

E. brunetti

COCCIVEX Pharmacodynamics
Amprolium is a thiamine (vitamin B1) analogue and is a competitive
antagonist of thiamine transport mechanisms.

Thiamin

The thiamin transport system in the parasite is 50 times more

sensitive than the hosts one. Consequently, the unicelular system of
the parasyte is more sensititve to amprolium.
Amprolium clearly shows a maximum activity at the third day of the
Eimeria cyclus. It is stated that it acts mainly on the first generation
schizonts, preventing the differentiation of the merozoites. The
evidence suggests that it also suppresses, in some degree, the sexual
stages gametogony and the sporulation of the oocysts.

COCCIVEX Pharmacokinetics

Amprolium is known to be slightly absorbed by oral route .

Total bioavailability can vary in fasted or non fasted broilers but the
absorption levels remain in the range 2 to 6%.

The absorption of AMPROLIUM varies from each intestinal section
to the other,
 91% (of max

6 %)

 < 10% (of max

Caecum.

in one hour in the duodenum

6 %) in

one hour in Jejunum, ileum and

Amprolium is excreted as a parent drug at levels of 45 to 64% .i

Hamamoto K, Koike R, Machida Y.Bioavailability of amprolium in fasting and nonfasting chickens after intravenous and oral administration. J
Vet Pharmacol Ther 2000 Feb;23(1):9-14

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COCCIVEX

Pharmakinetics

The Caecum : The main action area for Eimeria control

Pharmacokinetic studies prove that the absorption / presence of
amprolium varies from each intestinal section to the other. The
duodenum, jejunum and ileum present increasing amprolium
values, remaining the highest concentration unabsorbed in the
caecum.

Intestinal Amprolium concentration

g/g
700
600
500
400
300
200
100
0

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Duodenum

Jejunum

Ileum

Caecum

COCCIVEX Efficacy

Administered dose ml/litre of water

Group

Site A

Site B

Ref

2 ml Sulfadim

2 ml Sulfadim

Test

1 ml AMPROLIUM 20% oral solution

0.6 ml AMPROLIUM 20% oral solution

0.94 ml Placebo

0.6 ml placebo

Placebo

Duration of placebo and AMPROLIUM 20% oral solution treatments

was 7 days, and 6 days for Sulfadim.
Clinical observations were carried out after one week to determine
treatments safety.
Faeces state in each group was observed during this post-treatment
period, and signs of diarrhoea were not detected.

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COCCIVEX Efficacy
Results of % of recovery per groups of treatment

% Recovery
89,28

90
72,14

80
60

70
60
50

35,71

40
19,11

30
20
10

8,8
0

0
Da 0

Da 4

amprolium sp

Sulfadim

Da 7

Control

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COCCIVEX - ESP
COCCIBAL
BE-BG-DE-DK-EL-FR-HU-IT-LU-PL-PT-RO-UK

Target species: Broilers, replacement pullets, breedings hens,

laying hens, turkeys.
Indications : Treatment of coccidiosis.
Dose and administration :
Through drinking water : 20 mg / kg b.w. / day during 5 -7 days.
(Equivalent to 0,5 1 ml COCCIVEX / L. drinking water).
Cost-effective dosage pattern :
5 days 3 days rest - 5 days  [ 5 (3) 5 ]

Withdrawal time :
Broilers, breeding hens ; meat : 0 days
Laying hens ; eggs : 0 days
Turkeys ; meat : 0 days
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Recommendations for use

Broilers and replacement pullets / at incidence of coccidiosis
due to :
 Coccidiostat or Vaccination failure / resistance.
 Outbreak after in-feed coccidiostat withdrawal.
 Re-used litter.
 Increased environmental humidity (wet climates)
 Secundary Necrotic enteritis infections + environmental
factors.
 Doses: 1 ml/ L

(0,5 ml for pullets < 21 d)

Pattern : 5 days 3 days rest - 5 days  [ 5 (3) 5 ]

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Coccidiosis

ACTION SITES of Amprolium:

Inhibition takes place at Schizogony-Merogony and Gametogony phase.
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Recommendations for use

Laying hens ; coccidiosis outbreaks due to :
 Un-balance between bioburden and acquired immunity
+ housing / environmental factors.
 New animal welfare regulations may increase coccidia
incidence.
Dose: 1 ml/ L. water, during 5-7 das;
Recommended pattern : 5 - (3) - 5
Turkeys: coccidiosis outbreaks due to :
 Not frequent, though similar to broilers, often associated
to digestive pathologies.
 Non-protected after coccidiostat withdrawal.
 Dose : 1 ml/ L. water, same pattern.
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GRACIAS - THANK YOU

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