Transcript General

The using of sodium salicylate for
stress prevention, reducing
morbidity and mortality of the piglets
and complement treatment of
infectious pig diseases.
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History
In the 1st century AD Dioscorides, in the
first known pharmacopoeia, referred to
the medicinal properties of the willow
tree
 The first veterinary use of a synthetic
drug, the sodium salt of salicylic acid,
was reported in 1875.

P.Lees, J. vet. Pharmacol. Therap. 27, 479–490, 2004.
Registration

First choice oral NSAID with anti
inflammatory, anti pyretic and analgesic
properties, for early treatment of
infections in swine and calves, alone or
concurrent with antibiotic therapy.
NSAID’s mode of action
Cell damage
Corticosteroids
Phospholipids
Phospholipase
NSAIDs
Arachidonic acid
Cyclooxygenase
Prostaglandins
Lipoxygenase
Leucotriens
NSAID = Non Steroidal Anti-Inflammatory Drug
= without the immune-suppressive effect of corticosteroids
But NSAIDs do more
Tegeder et al.
 Federation of American Societies for
Experimental Biology Journal
 Vol 15 October 2001 , p 2060
( 99 references on sodium salicylate in
this article)

E.coli does increase cAMP in the
intestines. Sodium salicylate does
reduce the amount of fluid.
 Therefore less loss of fluid in case of
diarrhoea.

Josef Szancer Dansk VetTidsskr., 1980,63,3, 1/2
Salicylates
Sodium salicylate (Solacyl) belongs to the
group of salicylates.
 Salicylates act through the active salicylic
acid, which binds COX (Higgs, Proc. Acad.
Sci. USA 1987)
 Salicylates have several effects:

– Antipyretic
fight fever
– Anti-inflammatory fight inflammation
– Analgesic
fight pain
T.D. WARNER and co-workers
 Proc. Natl. Acad. Sci. USA
 Vol. 96, pp. 7563–7568, June 1999
 Pharmacology

Chemistry
SS. By acidification of the sodium salt we get salicylic acid.
This is an acid-base reaction.
Sodium salicylate
Salicylic acid
ASA. Before we get salicylic acid from acetyl salicylic acid, it has to
be deacetylated. Hydrolysis of aspirin to salicylic acid by
nonspecific esterases occurs in the liver and, to a lesser extent in
the stomach (Clin Pharmacokinet. 1985 Mar-Apr;10(2):164-77.)
Aspirin
hydrolysis
Salicylic acid
To: Vet. applied pharmacology and therapeutics, Brander et al, 5th ed 1991
Differences ASA-SS
Aspirine has effect on trombocyte
aggregation due to de-acetylating effect
(hydrolysation) needed to produce
salicylate (Oberdisse, 2002), Sodium
salicylate not.
Acetyl group binds with thromboxane
enzyme
High bioavailability
DOSAGE IV calf
ss 35-40 SS
mg/kg
Oral calf
SS
IV pig SS Oral pig
SS
Cmax
(mg/L)
53,98
92,10
Tmax (h)
1,97
1,07
IV
poultry
SS
<10
T1/2 (h)
1,23
1,17
1,15
1,23
4,04
Vd (l/kg)
0,24
0,30
0,19
-
0,39
BA (%)
77,8
103
Swine and calve: Summary report: Sodium salicylate (extension to oral use in bovine and porcine)
EMEA/MRL/897/04-FINAL
Cattle: Coetzee et al, 2007, JVPT.
Poultry: Baert et al, JVPT 25; 449-453
Oral
cattle
ASA
Coetzee
50mg/kg
LOW
Plasma levels correspond to
in water dosage

When a dosage of 12mg/kg BW is targeted, which is reached by 118mg/L
therapeutic solution, a plasma level of 7,2 mg/L will be reached as shown in
table

Patterson et al, Journal of Swine Health and Production — Volume 15, Number 3

T4 = 118,5mg/L SS in water corresponds with a targeted dose of 11.85mg/kg BW targeted dose
Calculations based on full dissolution and a stable solution for 24 hrs.

Pulse dosing plasma levels high
Mg/L
120
100
80
12 mg/kg cont
60
35 mg/kg cont
35 mg/kg 1dd pulse
40
17,5 mg/kg 2dd pulse
20
0
t = 0 t=1
Efficacy treshold to
affect cortisol levels
acc Coetzee
t=2
t=4
t=6
.
t=8 t=10 t=12 t=14 t=18 t=19 t=20 t=21 t=22 t=23 t=24
-20
1. Cmax 92,10mg/L at dose of 35mg/kg (EMEA summary report)
2. The post NSAID effect will linger on until 5 µg/L Coetzee et al, 2007, JVPT.
3. If necessary, antibiotic treatment can be given between the Solacyl pulses
Result for the pigs
Continue to eat and drink
 Less disturbed by pen mates
 More mobile

Tolerance
Pigs tolerate dosages up to 175 mg/kg
for up to 10 days without any significant
adverse effects.
 Sodium salicylate has been reported to
inhibit the formation of gastric
ulcerations induced by aspirin,
indomethacin, and absolute ethanol.
(Adcock JE, Life Sci. 1983 Jun
20;32(25):2905-10 )

Solacyl
Solacyl – indications
Calves:
 Supportive treatment for reduction of
pyrexia in acute respiratory disease, in
combination with appropriate (e.g. antiinfective) therapy if necessary.
Pigs:
 For the treatment of inflammation, in
combination with a simultaneous
antibiotic therapy.
Solacyl 100 % - dosing
Calves: 40 mg sodium salicylate per kg
body weight, once daily during 1 to 3 days.
 Application: orally via drinking water or
milk (substitute).
 Swine: 35 mg sodium salicylate per kg
body weight per day, during 3 to 5 days.
 Application: orally via drinking water

Solacyl – major practical use
according swine veterinarians
In order of importance:
 Respiratory infections ( sometimes
alone preventively, sometimes
curatively with an antibiotic)
 Vaccination reactions ( prevention and
curatively); most of the time it is known
which vaccines give problems on which
farms; mostly with Bordetella vaccines.
Solacyl – minor practical use
according swine veterinarians
Oedema disease ( therapeutically with
antibiotics)
 Streptococcus suis (therapeutically with
antibiotics)
 In the prevention of PSE meat or heart
failure in heterozygote positive stress
swine (Solacyl alone)
 Treatment of sick animals immediately
before slaughter to prevent mortality
and cannibalism. With Solacyl the
animals continue to eat and are able to
defend themselves.

Solacyl – pulse medication

Alternatively Solacyl can also be
administered with the drinking water as
pulse medication. Half of the calculated
total daily amount of powder is mixed with
5-10 litres of clean water and stirred until
evenly dispersed. This solution is then
added, whilst stirring, into an amount of
drinking water that will be consumed within
approximately 3-4 hours and administered
twice daily.
Solacyl - dosage

Rinse pipes during 1 to 2 hours between
Solacyl and other medication through the
water
Solacyl - withdrawal
Pigs: meat and offal: zero days
 Calves: meat and offal: zero days
 Do not use in cows producing milk for
human consumption.

Product
Active
Characteristics
Activities
Acetylsalicylic
acid
salicylate
Insoluble
More Cox 1
Antiinflammatory
Antipyretic
Analgesic
Sodium
salicylate
salicylate
Soluble
More Cox 2
Antiinflammatory
Antipyretic
Analgesic
Paracetamol
paracetamol Insoluble
Antipyretic
Solacyl - aspirine








Excellent solubility
High bio-availability
Low dosing for cattle
Less stomach
ulcers, stomach
bleedings
Fast action
More Cox 2
Little influence on
coagulation
0 days withdrawal






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Little soluble
Low bio-availability
High dosing in cattle
Slow action
More COX 1
Influence on
coagulation
No withdrawal ….
Product characteristics
1 kg 100% powder in alu-foil bags
 Carton secondary packing to hold 6
bags
 Excellent water solubility
 Stability in hard water
 Stability in acidified water
 Stability in wet feed
 Stability in milk
 Stability in the unopened bag
 Stability in the opened bag

Water solubility
ASA 3,33 g per L the highest
achievable dose of ASA in swine would
be 3,1 mg per kg per day = not
efficacious
 SS 1111,1 g per L  efficacious doses
can be reached in plasma.


Budavari S, O’Neil MJ, Smith A, Heckelman PE, eds. The Merck Index: An Encyclopedia of
Chemicals, Drugs, and Biologicals. 11th ed. Rahway, New Jersey: Merck and Company Inc;
1989:1367–1368.
Stability in water
a therapeutic solution of 350 mg per I
water (therapeutic)
 a concentrated solution of 35 g per I
water (stock)
 a concentrated solution of 105 g per I
water (pulse stock)

Stability in water
Conclusions of these studies are that
solubility and stability in both hard and
soft water is very good. Solubility is no
problem: in this study it was shown that
up to 100g/L is dissolved in a few
seconds.
 24 hours after dissolution we still find
100% of the compound back when
analysed.

Stability in water - pH

When dissolved in hard water that has a
pH of about 8,5 pH will drop a little to
around 8. In soft water of pH 6 it also
remains clear and stable in solution.
Stability in wet feed
It has been demonstrated that sodium
salicylate is stable for 24 hours in wet
feed (30ºC, low pH) obtained from a
commercial farm
SOLACYL
technical training
Solacyl 100 %
100% Sodium salicylate
Thanks for your attention